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CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Clinical Hx: Collected:

Male

Female

Male

Female

Accession Number: CGI ID No: Ordering Physician: Client: Accession Number: Client CGI ID No: ClientPhysician: Address: Ordering Telephone: Client: Client ID No: Client Address: Telephone:

Received: Reported: Clinical Hx:

Σ Summation Report

FINAL DIAGNOSIS:

Σ Summation Report

CLINICAL DATA: CLL. No CBC information provided.

A monoclonal population sLambda+, CD20+, CD5+, CD10-, CLL. NoofCBC informationCD19+, provided. CLINICAL DATA: CD23+, CD11c-, B cells detected by flow cytometry analysis, 59% of FINAL DIAGNOSIS: lymphocytes, 20% of total cells, consistent with B-cell chronic lymphocytic leukemia, CD38-, ZAP70+, with mutated IGHV, andCD10-, A monoclonal population of sLambda+, CD19+, CD20+, CD5+, abnormal karyotype including deletions of ATM and 13q14. CD23+, CD11c-, B cells detected by flow cytometry analysis, 59% of Negative for TP53, NOTCH1 mutations. lymphocytes, 20% SF3B1, of total or cells, consistent with B-cell chronic lymphocytic leukemia, CD38-, ZAP70+, with mutated IGHV, and abnormal karyotype including deletions of ATM and 13q14. COMMENTS: Negative foris TP53, SF3B1, NOTCH1prognosis mutations. Loss of ATM associated with or unfavorable in CLL. Clinical correlation

and follow up is recommended. COMMENTS: Loss ofCYTOMETRY: ATM is associated with unfavorable prognosis in CLL. Clinical correlation FLOW and follow up is recommended. A monoclonal population of sLambda+, CD19+, CD20+, CD5+, CD10-, CD23+, CD11c-, CD38- B cells detected, 59% of lymphocytes, 20% of total cells, consistent with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, FLOW CYTOMETRY: CD38-, ZAP70+. A monoclonal population of sLambda+, CD19+, CD20+, CD5+, CD10-, CD23+, CD11c-, CD38- B cells detected, 59% of lymphocytes, 20% of total cells, KARYOTYPE: consistent with B-cell chronic lymphocytic leukemia/small lymphocytic 46,XX,del(11)(q21q23),ins(13;?)(q14:?)[13]/46,XX[7] Abnormal Femalelymphoma, Karyotype CD38-, ZAP70+. FISH: KARYOTYPE: Abnormal CLL FISH Panel with deletion of 13q14 (on one 13) seen in 34% cells. 46,XX,del(11)(q21q23),ins(13;?)(q14:?)[13]/46,XX[7] Abnormal Female Karyotype Also, there was seen deletion of ATM gene on 11q22.3 in 32% cells. FISH: MOLECULAR: Abnormal CLL FISH Panel with deletion of 13q14 (on one 13) seen in 34% cells. IGHV Mutation Status: Mutated Also, there was seen deletion IGHV Family: V4-61 of ATM gene on 11q22.3 in 32% cells. Functionality: Productive MOLECULAR: Mutation Frequency: 3.8% IGHV Mutation Status: Mutated MatBA®-CLL Array-CGH: A low level loss of 11q and 13q was observed in the IGHV Family: V4-61 MatBA® Functionality: analysis. Only Productive a small population of cells carries these aberrations. It is belowMutation the sensitivity to score3.8% positive. Frequency: TP53 Mutation Assay: Negative TP53 ® level lossmutation. of 11q and 13q was observed in the MatBA -CLL Array-CGH: A low for NOTCH1 Mutation Assay: Negative for NOTCH1 MatBA® analysis. Only a small population of cells mutation. carries these aberrations. It SF3B1 Assay:toNegative for SF3B1 mutation. is belowMutation the sensitivity score positive. TP53 Mutation Assay: Negative for TP53 mutation. NOTCH1 Mutation Assay: Negative for NOTCH1 mutation. SF3B1 Mutation Assay: Negative for SF3B1 mutation.

Flow Plot CD5 vs CD19

Flow Plot CD5 vs CD19

46,XX,del(11)(q21q23),ins(13;?)(q 14:?) 46,XX,del(11)(q21q23),ins(13;?)(q 14:?)

FISH 11q22.3(1 green)/ 17p13.1(2 red) FISH 11q22.3(1 green)/ 17p13.1(2 red)

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM Patient Name: Sex: Date of Birth: Specimen: Collected: Received: Patient Name: Reported: Sex: Date of Birth: Specimen: Collected: Interpretation: Received: Reported: Comments:

Male

Female

Female

Accession Number: CGI ID No: Ordering Physician: Client: Client ID No: ClientNumber: Address: Accession Telephone: CGI ID No:

Ordering Physician:

FLOW CYTOMETRY REPORT Client:

ClientCD20+, ID No: CD5+, CD10-, CD23+, A monoclonal population of sLambda+, CD19+, Client Address: CD11c-, CD38- B cells detected, 59% of lymphocytes, 20% of total cells, Telephone: consistent with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, CD38-, ZAP70+ (see comment).

FLOW CYTOMETRY REPORT

Interpretation:

ZAP70+ B-cells comprise 45% of CLL cells, with the B-cell to T-cell mean fluorescence intensity of 0.78. Correlation with of IGHV mutation status is recommended. Aratio monoclonal population sLambda+, CD19+, CD20+, CD5+, CD10-, CD23+, Clinical correlation follow-up is recommended. CD11c-, CD38- Band cells detected, 59% of lymphocytes, 20% of total cells,

consistent with 88% B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, Viability (7-AAD): Differential Cell Count : comment). Lymphocytes 36 % CD38-, ZAP70+ (see

Results: Comments: Results:

Male

Monocytes 6% ZAP70+ B-cells comprise 45% of CLL cells, with the B-cell to T-cell mean fluorescence intensity Granulocytes 54 % ratio of 0.78. Correlation with IGHV mutation status is recommended. BLASTS 0% Clinical correlation and follow-up is recommended. Plasma Cells 0.00 % Viability (7-AAD): 88% Abnormal cell population: Present Differential Cellsize: Count : Lymphocytes 36 % Abnormal cell Small Monocytes 6% T/NK antigens B-cell antigens 54 % Myeloid/Other antigens Granulocytes (lymphocyte gate) (lymphocyte gate) (open gate) BLASTS 0 % CD3 29% CD19 63% CD45 95% Plasma 0.00 % CD7 31% CD20Cells 61% Abnormal cell population: Present CD5 32% CD19+sKappa 2% CD2 34%Small CD19+sLambda 59% Abnormal cell size:

CD3+CD4 T/NK antigens CD3+CD8 (lymphocyte gate) CD56+CD3CD3 CD57 CD7 CD5 CD2 CD3+CD4 CD3+CD8 CD56+CD3CD57

24% 3% 4% 29% 4% 31% 32% 34% 24% 3% 4% 4%

CD19+CD5 B-cell antigens CD20+CD10 (lymphocyte gate) CD19+CD11c CD19 CD19+CD38 CD20 CD19+CD23 CD19+sKappa ZAP70 (CLL) CD19+sLambda CD19+CD5 CD20+CD10 CD19+CD11c CD19+CD38 CD19+CD23 End of Report ZAP70 (CLL)

58% 0.1% 5% 63% 4% 61% 45% 2% 45% 59% 58% 0.1% 5% 4% 45% 45%

Myeloid/Other antigens (open gate) CD45

95%

End of Report

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM

Patient Name: Accession Number: Sex: CGI ID No: Male Female Date of Birth: Ordering Physician: Specimen: Client: Patient Name: Accession Number: Collected: Client ID No: Sex: CGI ID No: Male Female Received: Client Address: Date of Birth: Reported: OrderingTelephone: Physician: Specimen: Client: Collected: Client CYTOGENETICS REPORTID No: Received: Client Address: Reported: Procedure: GTG-banding Metaphases analyzed and cells counted: 20/50 Telephone: Chromosome band-resolution: 400-450 Metaphases Karyotyped: 3 Culture: 24 Hr. Unstimulated and 72 Hr. Stimulated Metaphases Captured: 5 CYTOGENETICS REPORT w/ DSP30/IL-2 Procedure: GTG-banding Metaphases analyzed and cells counted: 20/50 Karyotype: Chromosome band-resolution: 400-450 Metaphases Karyotyped: 3 46,XX,del(11)(q21q23),ins(13;?)(q14:?)[13]/46,XX[7] Culture: 24 Hr. Unstimulated and 72 Hr. Stimulated Metaphases Captured: 5 Summary:w/ DSP30/IL-2 Abnormal Female Karyotype

46,XX,del(11)(q21q23),ins(13;?)(q14:?)[13]/46,XX[7] Cytogenetic analysis revealed deletion of long arm (q) of chromosome 11 and insertion in chromosome material of unknown origin at q14 region of chromosome 13 in 13 of the 20 Summary: Abnormal Female Karyotype cells analyzed. 11q deletion is associated with adverse prognosis in CLL. analysis deletion of long arm (q) of chromosome 11 and insertion in Interpretation: Cytogenetic Please see the FISH revealed results (FH13-000942). chromosome material of unknown origin at q14 region of chromosome 13 in 13 of the 20 cells analyzed. The results of this analysis do not exclude the possibility of genetic alterations below the band-resolution of this test or abnormalities dueis to associated other etiologies.with adverse prognosis in CLL. 11q deletion Please see the FISH results (FH13-000942). Karyotype: Interpretation:

The results of this analysis do not exclude the possibility of genetic alterations below the band-resolution of this test or abnormalities due to other etiologies.

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 2 The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 2


CLL CompleteSM

Patient Name:

Accession Number:

Karyotype: 46,XX,del(11)(q21q23), ins(13;?)(q14:?) Patient Name:

Accession Number:

Karyotype: 46,XX,del(11)(q21q23), ins(13;?)(q14:?)

End of Report

End of Report

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 2 of 2

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 2 of 2


CLL CompleteSM

200

ABNORMAL ABNORMAL

PROBE SETS 11q13 (CCND1), 14q32 CHROMOSOME (IGH) LOCI

FLUORESCENCE IN SITU HYBRIDIZATION REPORT NORMAL -------------------------------------------

PROBE SETS CHROMOSOME LOCI

Female

-------------------------------------------

Specimen: Collected: Received: Reported:

Accession Number: CGI ID No: Ordering Physician: Client: Client ID No: Accession Number: Client Address: CGI ID No: Male Female OrderingTelephone: Physician: Client: Client ID No: FLUORESCENCE IN SITU HYBRIDIZATION REPORT Client Address: FISH Probes*: CLL [Abbott (Vysis), Inc.] Telephone:

Male

# CELLS # CELLS ANALYZEDANALYZED

Patient Name: Sex: Date of Birth: Specimen: Collected: Patient Name: Received: Sex: Reported: Date of Birth:

---

CUTOFF FISH Probes*: CLL [Abbott (Vysis), Inc.] RESULTS VALUE (95% CI) NORMAL CUTOFF t(11;14) ≥ 1% VALUE (95% CI)

NormalRESULTS Signal Pattern

ISCN NOMENCLATURE 2009

ISCN NOMENCLATURE 2009 nuc ish(CCND1x2,IGHx2)[200]

Del 11q22.3 > 6% Abnormal Signal Pattern nuc ish(ATMx1,TP53x2)[64/200] Del 17p13 > 7% 200 --t(11;14) ≥ 1% Normal Signal Pattern nuc ish(CCND1x2,IGHx2)[200] Gain of 12 > 2.5% > Del 11q22.3 nuc 11q22.3 (ATM), 17p13 Del 13q 6%> 5.5% Abnormal nuc ish(ATMx1,TP53x2)[64/200] 200 64 CEP Abnormal Signal Signal Pattern ish(CEP12x2,D13S319x0,13q34x2)[35/200] (p53)12, 200 68 Homozygous Del 17p13 > 7% 13q14(D13S319),13q34 Patterns nuc Del 13q > 1.5% ish(CEP12x2,D13S319x1,13q34x2)[33/200] Gain of 12 Loss 13 > 2.5% 5.5% nuc Del 13q > 5.5% CEP 12, Abnormal Signal ish(CEP12x2,D13S319x0,13q34x2)[35/200] CEP6(D6Z1), 6q22Del(6q22-23) ≥ Homozygous 200 68 200 --Normal nuc nuc ish(D6Z1x2,MYBx2)[200] 13q14(D13S319),13q34 PatternsSignal Pattern 23(MYB) 3%> 1.5% Del 13q ish(CEP12x2,D13S319x1,13q34x2)[33/200] Loss of 13 > * FISH only testing is not equivalent to conventional cytogenetic analysis of the patient’s specimen, and is limited to the specific 5.5% probe(s) and their corresponding DNA locations (genes) only. CEP6(D6Z1), 6q22Del(6q22-23) ≥ 200 --Normal Signal Pattern nuc ish(D6Z1x2,MYBx2)[200] 23(MYB) 3% 11q22.3 (ATM), 17p13 (p53) 11q13 (CCND1), 14q32 (IGH)

200

64

* FISH only testing is not equivalent to conventional cytogenetic analysis of the patient’s specimen, and is limited to the specific probe(s) and their corresponding DNA locations (genes) only.

FISH testing for HER2/neu breast cancer (PathVysion), ALK-Break Apart test for Non-Small Cell Lung Cancer (NSCLC), EGR1 for myelodyplastic syndrome, TP53/ATM & D13S319/13q34/ D12Z3for chronic lymphocytic leukemia and X/Y probes for bone marrow transplant have been approved by Food & Drug Administration (FDA) as in vitro diagnostic (IVD) tests. The tests utilizing analyte-specific reagents (ASRs) were developed & their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA ’88 regulations. They have not been cleared or approved by for specific uses by the Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics Inc., 201, Route 17 North, Rutherford, NJ 07070. Phone Number: (888) 334-4988 CLIA#: 31D1038733 CAP LAP#: 7191582 FISH testing for HER2/neu breast cancer (PathVysion), ALK-Break Apart test for Non-Small Cell Lung Cancer (NSCLC), EGR1 for myelodyplastic syndrome, TP53/ATM & D13S319/13q34/ Page 1 of 2 D12Z3for chronic lymphocytic leukemia and X/Y probes for bone marrow transplant have been approved by Food & Drug Administration (FDA) as in vitro diagnostic (IVD) tests. The tests utilizing analyte-specific reagents (ASRs) were developed & their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA ’88 regulations. They have not been cleared or approved by for specific uses by the Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics Inc., 201, Route 17 North, Rutherford, NJ 07070. Phone Number: (888) 334-4988 CLIA#: 31D1038733 CAP LAP#: 7191582

Page 1 of 2


CLL CompleteSM Patient Name:

Accession Number:

Summary:

Abnormal CLL FISH Panel

Final Interpretation: Patient Name:

This FISH analysis showed abnormal signal patterns with 13q14/13q34 probe set showing clonal Accession Number: evolution from heterozygous deletion of 13q14 (on one 13) to homozygous deletion (on both 13s), seen in 34% cells.

Summary: Final Interpretation:

Abnormal CLL FISH Panel

Also, there was seen deletion of ATM gene on 11q22.3 in 32% cells. Both of the FISH findings are consistent with an evolving adverse prognosis CLL. This FISH analysis showed abnormal signal patterns with 13q14/13q34 probe set showing clonal evolution from heterozygous deletion of 13q14 (on one 13) to homozygous deletion (on both 13s), seen in 34% cells. Also, there was seen deletion of ATM gene on 11q22.3 in 32% cells. Both of the FISH findings are consistent with an evolving adverse prognosis CLL.

11q13(2 red)/ 14q32(2 green)

11q22.3(1 green)/ 17p13.1(2 red)

CEP12 (2 green)/13q14 (0 red)/13q34 (2 aqua)

CEP12 (2 green)/13q14 (1 red)/13q34 (2 aqua)

CEP 6 (2 green)/6q23 (2 red)

Representative FISH images of the CLL panel probe sets. 11q22.3(1 green)/ CEP 6 (2 green)/6q23 11q13(2 red)/ CEP12 (2 CEP12 (2 FISH analysis can only identify abnormalities that are within the specificgreen)/13q14 locus of the probe(s) may not detect(1 small clonal populations (2 red)of aberrant (0 used and green)/13q14 17p13.1(2 red) 14q32(2 green) cells below the normal cut-off values; therefore, FISH results should be interpreted in the context of the patient’s full clinical history and under most red)/13q34 (2 aqua) red)/13q34 (2 aqua) circumstances, in conjunction with metaphase chromosome analysis. Representative FISH images of the CLL panel probe sets. FISH analysis can only identify abnormalities that are within the specific locus of the probe(s) used and may not detect small clonal populations of aberrant cells below the normal cut-off values; therefore, FISH results should be interpreted in the context of the patient’s full clinical history and under most circumstances, in conjunction with metaphase chromosome analysis. End of Report

End of Report

FISH testing for HER2/neu breast cancer (PathVysion), ALK-Break Apart test for Non-Small Cell Lung Cancer (NSCLC), EGR1 for myelodyplastic syndrome, TP53/ATM & D13S319/13q34/ D12Z3for chronic lymphocytic leukemia and X/Y probes for bone marrow transplant have been approved by Food & Drug Administration (FDA) as in vitro diagnostic (IVD) tests. The tests utilizing analyte-specific reagents (ASRs) were developed & their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA ’88 regulations. They have not been cleared or approved by for specific uses by the Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics Inc., 201, Route 17 North, Rutherford, NJ 07070. Phone Number: (888) 334-4988 CLIA#: 31D1038733 CAP LAP#: 7191582

Page 2 of 2

FISH testing for HER2/neu breast cancer (PathVysion), ALK-Break Apart test for Non-Small Cell Lung Cancer (NSCLC), EGR1 for myelodyplastic syndrome, TP53/ATM & D13S319/13q34/ D12Z3for chronic lymphocytic leukemia and X/Y probes for bone marrow transplant have been approved by Food & Drug Administration (FDA) as in vitro diagnostic (IVD) tests. The tests utilizing analyte-specific reagents (ASRs) were developed & their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA ’88 regulations. They have not been cleared or approved by for specific uses by the Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics Inc., 201, Route 17 North, Rutherford, NJ 07070. Phone Number: (888) 334-4988 CLIA#: 31D1038733 CAP LAP#: 7191582

Page 2 of 2


CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Collected: Received: Reported: Results:

Results: Interpretation: Description: Interpretation: Description:

Accession Number: CGI ID No: Ordering Physician: Client: Accession Number: Client ID No: CGI ID No: Male Female Client Address: Ordering Physician: Telephone: Client: Client ID No: IGHV MUTATION ANALYSIS REPORT Client Address: Telephone: IGHV Family: V4-61 Functionality: Productive IGHV MUTATION ANALYSIS REPORT Mutation Frequency: 3.8% IGHV Family: V4-61 Mutated Functionality: Productive Mutation Frequency: 3.8%

Male

Female

The mutation status of the unique immunoglobulin gene (IGHV) rearrangement in the monoclonal proliferation of B-cells in chronic lymphocytic leukemia (CLL) is considered to have prognostic value. If mutations are detected at a level of 2% or higher in the sequenced V region of the clonal rearrangement, Mutated then the result is interpreted as "Mutated". If mutations are detected at a level below 2% in the sequenced V region of thestatus clonalofrearrangement, then the result is interpreted as "Unmutated". Those patients with a The mutation the unique immunoglobulin gene (IGHV) rearrangement in the monoclonal mutated IGHV gene usually havelymphocytic a less aggressive and(CLL) moreisindolent disease, withprognostic longer overall survival. proliferation of B-cells in chronic leukemia considered to have value. If Those patients with an unmutated usually a more V aggressive disease shorter overall mutations are detected at a level ofIGHV 2% orgene higher in thehave sequenced region of the clonaland rearrangement, survival. then the result is interpreted as "Mutated". If mutations are detected at a level below 2% in the sequenced V region of the clonal rearrangement, then the result is interpreted as "Unmutated". Those patients with a This assay utilizes to detect IGHV rearrangement sequence analysis to mutated IGHV genePCR usually have a a monoclonal less aggressive and more indolentfollowed disease,bywith longer overall survival. determine the specific familyIGHV and mutation frequency. sensitivity of the assayand is 10%. Samples Those patients with anIGHV unmutated gene usually have aThe more aggressive disease shorter overall in which the monoclonal B-cells are present at less than 10%, a specific IGHV rearrangement will not be survival. detected and will be reported as failures. This assay utilizes PCR to detect a monoclonal IGHV rearrangement followed by sequence analysis to determine the specific IGHV family and mutation frequency. The sensitivity of the assay is 10%. Samples in which the monoclonal B-cells are present at less than 10%, a specific IGHV rearrangement will not be detected and will be reported as failures.

End of Report

End of Report

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1 The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Clinical Hx: Collected: Received: Reported: Clinical Hx: Results:

Male

Female

Male

Female

MATBA速-CLL/SLL 速 Genomic Aberration MATBA -CLL/SLL

Loss of 8p Results:

Interpretation:

Interpretation: Description:

Description:

Loss of 11q (ATM) Genomic Aberration Loss of 13q (MIR15A/16-1)

Accession Number: CGI ID No: Ordering Physician: Client: Accession Number: Client ID No: CGI ID No: Client Address: OrderingTelephone: Physician: Client: Client ID No: ARRAY-CGH REPORT Client Address: Telephone: Result for Aberration ARRAY-CGH REPORT Negative

Negative ResultNegative for Aberration

8p (RB1) Loss of 13q

Negative

11q (TP53) (ATM) Loss of 17p Loss of 2p 13q (MIR15A/16-1) Gain

Negative Negative

Loss of 3q 13q (RB1) Gain Loss of 8q 17p (TP53) Gain

Negative Negative

2p Gain of 12 Gain of 3q

Negative Negative

Gain of 12

Negative

No copy number aberrations detected. Gaingenomic of 8q Negative Comment: A low level loss of 11q and 13q was observed in the MatBA analysis. Only a small population of cells carries these aberrations. It is No genomic copy number aberrations detected. below the sensitivity to score positive. Comment: A of low level loss regions of 11q 13q was observed in the MatBA The gain and loss specific genomic in and the monoclonal proliferation of B-cells in chronic analysis.leukemia/small Only a small population of (CLL/SLL) cells carries thesetoaberrations. It is lymphocytic lymphocytic lymphoma are considered have diagnostic and prognostic value. Loss of 13q at locus (MIR15A/16-1) below the sensitivity toone score positive. or both loci (MIR15A/16-1 and RB1) is observed in approximately 50% of CLL/SLL patients and as the sole abnormality is associated with a longer overall survival. patients with loss of 17p (TP53) (ATM) in general, haveofaB-cells shorterinoverall survival. The gain Those and loss of specific genomic regions inor the11q monoclonal proliferation chronic Other aberrations are variously observed in CLL/SLL patients with suggested prognostic value. lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are considered to have diagnostic and

prognostic value. Loss of 13q at one locus (MIR15A/16-1) or both loci (MIR15A/16-1 and RB1) is observed This assay utilizes microarray-based comparative genomic hybridizationis(array-CGH) to simultaneously in approximately 50% of CLL/SLL patients and as the sole abnormality associated with a longer overall detect theThose gain and loss with of multiple specimen DNA. Quantitative PCR is used to confirm survival. patients loss ofloci 17pin(TP53) or 11q (ATM) in general, have a shorter overallthe survival. detected genomic are gains and losses. The sensitivity ofpatients the assay is suggested 30-40%. Samples in which Other aberrations variously observed in CLL/SLL with prognostic value.the monoclonal B-cells are present at less than 30-40%, aberrations may not be detected and will be reported as noassay aberrations This utilizesdetected. microarray-based comparative genomic hybridization (array-CGH) to simultaneously detect the gain and loss of multiple loci in specimen DNA. Quantitative PCR is used to confirm the detected genomic gains and losses. The sensitivity of the assay is 30-40%. Samples in which the monoclonal B-cells are present at less than 30-40%, aberrations may not be detected and will be reported as no aberrations detected.

End of Report

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have End of Report not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1 The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Clinical Hx: Collected: Received: Reported: Clinical Hx: Results:

Male

Female

Male

Female

NOTCH1 MUTATION

Accession Number: CGI ID No: Ordering Physician: Client: Accession Number: Client ID No: CGI ID No: Client Address: OrderingTelephone: Physician: Client: Client ID No: Client Address: ASSAY REPORT Telephone:

Exon 34 Nucleotide Change NOTCH1

Amino Acid Change Results:

None detected MUTATION ASSAY REPORT None detected Exon 34

Nucleotide Change

None detected

Interpretation:

Negative for NOTCH1 mutation Amino Acid Change None detected

Description:

NOTCH1 (TRANSLOCATION-ASSOCIATED NOTCH HOMOLOG, TAN1) is a member of the Notch receptor family. The gene has been mapped to chromosome 9q34.3 and contains 34 exons distributed over 58.3Kb of DNA. The Notchmutation signaling network is an evolutionarily conserved intercellular signaling Negative for NOTCH1 pathway which regulates interactions between physically adjacent cells.

Interpretation: Description:

NOTCH1 (TRANSLOCATION-ASSOCIATED NOTCH HOMOLOG, TAN1) is a member of the Notch Mutations in NOTCH1 are found in an estimated 5-12% of chronic lymphocytic leukemia (CLL) and 12% of receptor family. The gene has been mapped to chromosome 9q34.3 and contains 34 exons distributed mantle cell lymphoma (MCL) patients at diagnosis (1-3). More than 99% of the NOTCH1 mutations over 58.3Kb of DNA. The Notch signaling network is an evolutionarily conserved intercellular signaling reported to date in CLL and MCL occur in exon 34 within an ~630-bp region (assessed in the current pathway which regulates interactions between physically adjacent cells. assay). NOTCH1 mutations in exon 34 in previously untreated CLL patients have been reported to be associated with shorter time to first treatment and shorter overall survival (OS) (1, 2). In newly diagnosed Mutations in NOTCH1 are found in an estimated 5-12% of chronic lymphocytic leukemia (CLL) and 12% of MCL patients, NOTCH1 mutations have been associated with poor OS (3). mantle cell lymphoma (MCL) patients at diagnosis (1-3). More than 99% of the NOTCH1 mutations reported to date in CLL and MCL occur in exon 34 within an ~630-bp region (assessed in the current Genomic DNA is amplified by PCR followed by bi-directional sequencing of the NOTCH1 product. Results assay). NOTCH1 mutations in exon 34 in previously untreated CLL patients have been reported to be are reported as positive or negative for the detection of a mutation. Analytical sensitivity of this assay is associated with shorter time to first treatment and shorter overall survival (OS) (1, 2). In newly diagnosed 20% of mutant in a background of wild-type genomic DNA. A negative result cannot entirely exclude the MCL patients, NOTCH1 mutations have been associated with poor OS (3). presence of NOTCH1 mutation in the specimen. Mutation results should be interpreted in conjunction with other clinical information. Genomic DNA is amplified by PCR followed by bi-directional sequencing of the NOTCH1 product. Results are reported as positive or negative for the detection of a mutation. Analytical sensitivity of this assay is 20% of mutant in a background of wild-type genomic DNA. A negative result cannot entirely exclude the 1. Puente et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukemia. presence of NOTCH1 mutation in the specimen. Mutation results should be interpreted in conjunction with Nature. 2011; 475(7354):101-5. other clinical information. 2. Fabbri et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med. 2011; 208(7):1389-401. 3. Kridel et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell 1. Puente et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukemia. lymphoma. Blood 2012; 119(9): 1963-1971. Nature. 2011; 475(7354):101-5. 2. Fabbri et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med. 2011; 208(7):1389-401. 3. Kridel et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood 2012; 119(9): 1963-1971.

End of Report

End of Report

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1 The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Clinical Hx: Collected: Received: Reported: Clinical Hx: Results:

Male

Female

Male

Female

TP53 MUTATION

Accession Number: CGI ID No: Ordering Physician: Accession Number: Client: CGI ID No: Client Ordering ClientPhysician: Address: Client: Telephone: Client ID No: Client Address: Telephone: ASSAY REPORT

Exon 5-6

Exon 7-9

Amino Acid Change

None detected Exon 5-6

None detected Exon 7-9

Nucleotide Change

None detected

None detected

Interpretation:

None detected Negative for TP53 mutation

None detected

Description: Interpretation:

TP53 (Tumor Protein 53) is located at chromosome 17p13 and encodes for a transcription factor that responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, Negative for TP53 mutation senescence, DNA repair, or changes in metabolism. Somatic TP53 gene alterations including mutations and deletions are frequent in most human cancers and sometimes have prognostic value. TP53 (Tumor Protein 53) is located at chromosome 17p13 and encodes for a transcription factor that responds to diverse cellular stresses to regulate target genes that induce cellcommonly cycle arrest, apoptosis, In hematologic malignancies, the frequency of TP53 mutations is lower than observed in solid senescence, DNA repair, or changes in metabolism. Somatic TP53 gene alterations including mutations and tumors and usually ranges between 5-10% (1). More than 90% of the mutations in these malignancies have deletions are frequent in5-9 most human and sometimes have prognostic value.Large B-Cell Lymphoma been detected in Exons (2-10). In cancers Chronic Lymphocytic Leukemia (CLL), Diffuse

Results:

Description:

TP53 MUTATION ASSAY REPORT Nucleotide Change None detected None detected

Amino Acid Change

(DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Hairy Cell Leukemia (HCL), Multiple In hematologic the frequency of TP53 mutations is lower than commonly observed in solid Myeloma (MM),malignancies, Acute Lymphoblastic Leukemia (ALL), Myelodysplastic Syndrome (MDS), and Acute Myeloid tumors and usually ranges between 5-10% (1). More than 90% of the mutations in these malignancies have Leukemia (AML). The presence of TP53 mutations has been associated with unfavorable prognosis (poorer been detected in Exons 5-9 (2-10). In Chronic Lymphocytic Leukemia (CLL), Diffuse Large B-Cell Lymphoma overall response rates, shorter progression-free survival, and shorter overall survival) (2-10). (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Hairy Cell Leukemia (HCL), Multiple Myeloma (MM),isAcute Lymphoblastic Leukemia Syndrome Myeloid Genomic DNA extracted and amplified by PCR(ALL), usingMyelodysplastic two pairs of primers flanking(MDS), Exons and 5-9 Acute of TP53. Leukemia (AML). The presence of TP53 mutations hasResults been associated with prognosis Amplification products are sequenced bi-directionally. are reported asunfavorable positive or negative for(poorer the overall response rates, shorter progression-free survival, shorter overallinsurvival) (2-10).of wild-type detection of a mutation. Analytical sensitivity of this assayand is 25% of mutant a background

genomic DNA. A negative result cannot entirely exclude the presence of TP53 mutations in the specimen. Genomic DNA isshould extracted and amplified by PCR using two pairs of primers flanking Exons 5-9 of TP53. Mutation results be interpreted in conjunction with other clinical information. Amplification products are sequenced bi-directionally. Results are reported as positive or negative for the detection a mutation. sensitivity oflow thisincidence assay isof25% of mutant in a background of wild-type 1. Peller S,of Rotter V. TP53 Analytical in hematological cancer: mutations with significant clinical relevance. genomic DNA. negative result cannot entirely exclude the presence of TP53 mutations in the specimen. Hum Mutat. 2003;A21(3):277-84. Mutation should be interpreted with other clinical information. 2. Zenz T, results et al.TP53 mutation and survival in in conjunction chronic lymphocytic leukemia. J Clin Oncol. 2010; 28(29):4473-9.

3. Xu-Monette ZY, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated R-CHOP: reportinfrom an International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 1. Pellerwith S, Rotter V. TP53 hematological cancer: low incidence of mutations with significant clinical relevance. 2012;120(19):3986-96 Hum Mutat. 2003; 21(3):277-84. 4. Zenz O'Shea et al. The presence of survival TP53 mutation at diagnosis of follicular identifies high-risk group of 2. T, D, et al.TP53 mutation and in chronic lymphocytic leukemia.lymphoma J Clin Oncol. 2010; a28(29):4473-9. patients with shortened to disease progression and poorer overallofsurvival. 3. Xu-Monette ZY, et al.time Mutational profile and prognostic significance TP53 inBlood. diffuse2008; large112(8):3126-9. B-cell lymphoma patients 5. Halldórsdóttir AM, etreport al. Impact mutationDLBCL and 17p deletion in mantle cell lymphoma. Leukemia.2011; treated with R-CHOP: from of anTP53 International Rituximab-CHOP Consortium Program Study. Blood. 25(12):1904-84. 2012;120(19):3986-96 6. O'Shea König EA, in hairy leukemia. Leukemia. 2000;14(4):706-11 4. D, et et al. al. p53 The mutations presence of TP53 cell mutation at diagnosis of follicular lymphoma identifies a high-risk group of 7. Boyd KD, al. The clinical and molecular and biology of del(17p) in multiple myeloma with conventional or patients with et shortened time toimpact disease progression poorer overall survival. Blood. 2008;treated 112(8):3126-9. thalidomide-based therapy. GenesofChromosomes 50(10):765-74. 5. Halldórsdóttir AM, et al. Impact TP53 mutationCancer. and 17p2011; deletion in mantle cell lymphoma. Leukemia.2011; 8. Chiaretti S, et al. TP53 mutations are frequent in adult acute lymphoblastic leukemia cases negative for recurrent fusion 25(12):1904-84. genes and correlate with poor response induction therapy. Haematologica. 2013 Feb 12. 6. König EA, et al. p53 mutations in hairytocell leukemia. Leukemia. 2000;14(4):706-11 9. Jädersten M,al. et The al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.or J 7. Boyd KD, et clinical impact and molecular biology of del(17p) in multiple myeloma treated with conventional Clin Oncol. 2011 20;29(15):1971-9 thalidomide-based therapy. Genes Chromosomes Cancer. 2011; 50(10):765-74. 10.Chiaretti Mrózek S, K. et Cytogenetic, molecular genetic, and characteristics of acute myeloid leukemia with complex fusion 8. al. TP53 mutations are frequent in clinical adult acute lymphoblastic leukemia cases negative forarecurrent karyotype. Oncol. 2008;response 35(4):365-77. genes and Semin correlate with poor to induction therapy. Haematologica. 2013 Feb 12. 9. Jädersten M, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J End of Report Clin Oncol. 2011 20;29(15):1971-9 10. Mrózek K. Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex Semin Oncol. 2008; 35(4):365-77. The tests utilizing analyte-specific karyotype. reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are Report used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJEnd 07070.of Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL CompleteSM

Patient Name: Sex: Date of Birth: Specimen: Patient Name: Collected: Sex: Received: Date of Birth: Reported: Specimen: Clinical Hx: Collected: Received: Reported: Clinical Hx: Results:

Results: Interpretation:

Male

Female

Male

Female

Accession Number: CGI ID No: Ordering Physician: Client: Accession Number: Client ID No: No: CGI ID Client Address: Ordering Physician: Telephone: Client:

SF3B1 MUTATION

Client ID No: Client Address: ASSAY REPORT Telephone:

Exon 14

Exon 15-16

Amino Acid Change

None detected Exon 14

None detected Exon 15-16

Nucleotide Change

None detected

None detected

None detected mutation

None detected

SF3B1 ASSAY REPORT Nucleotide ChangeMUTATION None detected None detected

Amino Acid Change Negative for SF3B1

Description: Interpretation: Description:

Negative for SF3B1 mutation The Splicing factor 3B subunit 1 (SF3B1) gene encodes a 155kDa protein which together with splicing factor 3a and a 12S RNA unit, form the U2 small nuclear ribonucleoprotein complex (U2 snRNP). The gene (NM_012433.2) maps to chromosome 2q33.1 and contains 25 exons distributed over 43.11Kb.

SF3B1 mutations with a 1 frequency 3-17% in previously untreated (1-3) more The Splicing factoroccur 3B subunit (SF3B1) of gene encodes a 155kDa protein CLL whichpatients together withand splicing than of those to date (C-terminal region with hotspot codons 662, 666, factor95% 3a and a 12Sreported RNA unit, form are the in U2exons small14-16 nuclear ribonucleoprotein complex (U2 snRNP). The 700 742) (1-3). The presence of SF3B1 2q33.1 somaticand mutations in 25 CLL has been associated with overall geneand (NM_012433.2) maps to chromosome contains exons distributed over 43.11Kb. unfavorable outcome (shorter time to disease progression and poor overall survival) (1-3). SF3B1, NOTCH1, and TP53 mutations occur mostly in mutually-exclusive CLL specimens (1-3).(1-3) and more SF3B1 mutations occur with a frequency of 3-17% in previously untreated CLL patients than 95% of those reported to date are in exons 14-16 (C-terminal region with hotspot codons 662, 666, In myelodysplastic (MDS), SF3B1 somatic mutations occur with a frequency 25-30%, inwith particular 700 and 742) (1-3).syndrome The presence of SF3B1 mutations in CLL has beenofassociated overall myelodysplasia with ring sideroblasts (RS-MDS) where ~75% mutations (reviewed 4). More than unfavorable outcome (shorter time to disease progression andexhibit poor overall survival) (1-3). in SF3B1, 95% of SF3B1 mutations reported to date areininmutually-exclusive exons 14-16 (C-terminal region with hotspot codons 622, NOTCH1, and TP53 mutations occur mostly CLL specimens (1-3). 625, 662, 666, and 700) (4). The presence of SF3B1 somatic mutations in MDS has been associated with a predictivesyndrome value for (MDS), diseaseSF3B1 phenotype with ring sideroblasts (4). Inpositive myelodysplastic mutations occur with a frequency of 25-30%, in particular myelodysplasia with ring sideroblasts (RS-MDS) where ~75% exhibit mutations (reviewed in 4). More than Genomic DNA is extractedreported and amplified PCR using14-16 two pairs of primers flanking of 622, 95% of SF3B1 mutations to dateby are in exons (C-terminal region with Exons hotspot14-16 codons SF3B1. Amplification products arepresence sequenced bi-directionally. Results are positive or negative 625, 662, 666, and 700) (4). The of SF3B1 somatic mutations in reported MDS hasas been associated with for mutation detection. Analytical sensitivity of thiswith assay 20% of mutant a positive predictive value for disease phenotype ringissideroblasts (4).in a background of wild-type genomic DNA. A negative result cannot entirely exclude the presence of SF3B1 mutations outside Exons 14-16. Mutation should interpreted in conjunction clinicalflanking laboratory findings. Genomic DNA isresults extracted andbe amplified by PCR using two with pairsother of primers Exons 14-16 of SF3B1. Amplification products are sequenced bi-directionally. Results are reported as positive or negative 1. D, et al. Mutations of thesensitivity SF3B1 splicing lymphocytic leukemia:ofassociation forRossi mutation detection. Analytical of this factor assay in is chronic 20% of mutant in a background wild-type with progression fludarabinerefractoriness. Bloodthe 2011; 118(26):6904-6908. genomic DNA. A and negative result cannot entirely exclude presence of SF3B1 mutations outside Exons 2. Wang L, et al.results SF3B1should and other novel cancer genes in chronic lymphocytic leukemia.findings. The New 14-16. Mutation be interpreted in conjunction with other clinical laboratory England Journal of Medicine 2011;365(26):2497-506 3. V, al. et al. Exome sequencing mutationslymphocytic of the splicing factorassociation SF3B1 gene 1. Quesada Rossi D, et Mutations of the SF3B1identifies splicing recurrent factor in chronic leukemia: in chronic lymphocytic leukemia. Nature GeneticsBlood 2011;2011; 44(1):47-52. with progression and fludarabinerefractoriness. 118(26):6904-6908. 4. Cazzola et al. Biologic clinical of in somatic of SF3B1 in myeloid and 2. Wang L, M, et al. SF3B1 and and other novel significance cancer genes chronicmutations lymphocytic leukemia. The New lymphoid neoplasms. Blood 2013; 121(2):260-9. England Journal of Medicine 2011;365(26):2497-506 3. Quesada V, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nature Genetics 2011; 44(1):47-52. 4. Cazzola M, et al. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 2013; 121(2):260-9.

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1

The tests utilizing analyte-specific reagents (ASR) were developed and their performance characteristics determined by Cancer Genetics, Inc. as required by CLIA '88 regulations. They have not been cleared or approved for specific uses by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. Cancer Genetics, Inc., 201 Route 17 North, Rutherford, NJ 07070. Phone number: (888) 334 - 4988 CLIA#:31D1038733; CAP LAP#: 7191582

Page 1 of 1


CLL Complete Program - Sample Report