Prevalence of Clonal Hematopoiesis Mutations in Tumor-Only Clinical Genomic Profiling of Solid Tumors

Supplementary Online Content

Ptashkin RN, Mandelker DL, Coombs CC, et al. Prevalence of clonal hematopoiesis mutations in tumor-only clinical genomic profiling of solid tumors. JAMA Oncol. Published online June 5, 2018. doi:10.1001/jamaoncol.2018.2297

eFigure 1. Details of the KRAS mutation identified as CH-ST eFigure 2. Sequencing of matched tumor and tissue samples confirms CH derived origin of variant found with high VAF in blood eTable. List of cancer types included in the study along with patient counts, minimum age, median age, maximum age, and median tumor content for each cancer type

This supplementary material has been provided by the authors to give readers additional information about their work.

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eFigure 1. Details of the KRAS mutation identified as CH-ST. A) IGV tracks for KRAS G12R in the matched tumor (top) and peripheral blood samples (bottom). B) Clinical data for the tumor sample including all tumor somatic alterations C) Allele specific copy number analysis results by FACETS A B

C 3

0 CNLOR

-3

0 VALOR

-2

3 Number Integer Copy 1 0 Chromosome: 13579111315171921 KRAS

Downloaded From: https://jamanetwork.com/ on 09/26/2021 eFigure 2. Sequencing of matched tumor and tissue samples confirms CH derived origin of variant found with high VAF in blood . A) IGV tracks for BRCA2 p.Gln3156* in matched tumor (top) and peripheral blood (bottom) samples. B) Clinical data for the tumor sample including all tumor somatic alterations C) Allele specific copy number analysis by FACETS confirms retention of both alleles. D) Sanger sequencing traces from various matched paitent tissues demonstrate the variant is somatic in the blood.

A B Melanoma (tumor content: 50%) D BRCA2 c.9466C>T p.Gln3156*

Gene Variant change VAF in tumor ABL1 V722I 0.18 hg19 NOTCH3 P197L 0.20 Tumor GRIN2A R1067W 0.20 TERT Promoter 0.3 C > T 11% Blood MLL3 G2136E 0.5 NCOR1 T574I 0.51 TP53 R181C 0.54 Saliva BRAF V600E 0.64 STAG2 P987S 0.7

RIT1 Amplification Buccal

Blood Tumor C > T 34%

Normal colon

BRCA2 c.9466C>T p.Gln3156*

Chr 13

Downloaded From: https://jamanetwork.com/ on 09/26/2021 eTable. List of cancer types included in the study along with patient counts, minimum age,

median age, maximum age, and median tumor content for each cancer type

Median Age Median

at Blood Tumor

General Tumor Type Count Min_Age Draw Max_Age Purity

Non‐Small Cell Lung Cancer 2621 17.5 67.2 93.2 30

Breast Carcinoma 2505 14.7 56.6 96.6 40

Colorectal Cancer 1538 13.5 57.0 94.6 30

Prostate Cancer 1069 38.0 67.3 90.4 40

Pancreatic Cancer 969 5.0 65.2 89.4 30

Glioma 869 2.4 53.4 93.8 60

Soft Tissue Sarcoma 674 0.3 52.1 91.9 60

Melanoma 650 5.5 63.6 95.3 60

Endometrial Cancer 575 27.5 64.2 93.2 40

Bladder Cancer 560 26.2 67.5 89.0 40

Cancer of Unknown Primary 474 2.6 63.2 94.1 40

Renal Cell Carcinoma 469 7.5 59.5 86.8 60

Esophagogastric Carcinoma 432 19.1 60.1 88.0 30

Ovarian Cancer 427 16.5 60.4 90.7 50

Biliary Cancer 367 21.5 63.4 88.7 30

Germ Cell Tumor 361 2.1 34.3 69.6 40

Thyroid Cancer 308 13.2 63.8 88.9 60

Downloaded From: https://jamanetwork.com/ on 09/26/2021 Head and Neck Carcinoma 287 16.3 61.5 98.7 40

Gastrointestinal Stromal

Tumor 210 16.3 59.8 89.9 70

Mesothelioma 177 12.0 68.9 89.1 40

Skin Cancer, Non‐Melanoma 172 9.9 70.3 97.2 50

Hepatocellular Carcinoma 165 1.8 61.7 86.9 60

Salivary Carcinoma 157 17.9 58.3 80.8 60

Small Cell Lung Cancer 145 24.8 67.1 85.2 60

Uterine Sarcoma 130 23.5 56.3 82.7 70

Appendiceal Cancer 121 27.6 56.6 87.8 20

Embryonal Tumor 115 0.5 5.7 85.7 60

Gastrointestinal

Neuroendocrine Tumor 84 21.5 60.4 89.0 50

Osteosarcoma 80 8.0 22.5 80.7 60

Cervical Cancer 75 23.9 50.8 87.6 40

Small Bowel Cancer 63 36.1 58.4 87.6 30

Ewing Sarcoma 54 1.4 23.1 79.1 60

Meningothelial Tumor 49 29.3 57.4 82.5 70

Ampullary Carcinoma 45 32.4 66.4 82.0 40

Anal Cancer 45 32.0 61.2 80.2 40

Adrenocortical Carcinoma 44 18.5 54.9 75.8 70

Downloaded From: https://jamanetwork.com/ on 09/26/2021 Chondrosarcoma 42 14.0 52.1 79.3 50

Thymic Tumor 42 15.9 60.7 83.3 50

Nerve Sheath Tumor 35 15.4 43.9 88.0 70

Sex Cord Stromal Tumor 28 6.6 51.5 83.6 70

Sellar Tumor 27 6.1 49.5 70.9 60

Chordoma 26 25.2 60.7 84.6 50

Breast Sarcoma 24 16.4 55.9 88.2 40

Ependymomal Tumor 18 3.5 32.9 68.5 75

Retinoblastoma 15 0.1 2.8 9.7 60

Gestational Trophoblastic

Disease 14 23.9 35.4 57.7 55

Unknown 14 24.9 60.1 79.3 40

Miscellaneous

Neuroepithelial Tumor 12 21.8 46.8 62.1 60

Miscellaneous Brain Tumor 11 3.4 28.9 60.3 55

Wilms Tumor 11 3.0 7.0 28.1 60

Vaginal Cancer 10 38.7 65.2 86.8 40

Penile Cancer 8 51.5 68.3 71.4 40

Histiocytosis 7 1.8 57.2 82.7 20

Non‐Hodgkin Lymphoma 5 47.4 58.9 73.2 40

Pheochromocytoma 5 26.4 56.1 71.8 60

Downloaded From: https://jamanetwork.com/ on 09/26/2021 Pineal Tumor 4 15.0 43.8 66.7 85

Anal Gland Adenocarcinoma 4 54.2 60.6 65.0 35

Glioma, NOS 3 10.2 52.4 66.9 40

Mixed Cervical Carcinoma 3 40.9 47.5 60.4 20

Renal Non‐Clear Cell

Carcinoma 2 51.4 57.4 63.4 50

Anaplastic Pleomorphic

Xanthoastrocytoma 2 30.4 32.8 35.2 85

Primary CNS Melanoma 2 45.2 55.0 64.7 75

Smooth Muscle Neoplasm,

NOS 2 18.6 35.3 52.1 75

Adenocarcinoma In Situ 1 66.4 66.4 66.4 20

Breast Neoplasm, NOS 1 55.6 55.6 55.6 60

Cervical Endometrioid

Carcinoma 1 59.5 59.5 59.5 10

Diffuse Astrocytoma 1 33.9 33.9 33.9 30

Fibrothecoma 1 10.0 10.0 10.0 80

Ovarian Choriocarcinoma,

NOS 1 28.2 28.2 28.2 20

Peritoneal Serous Carcinoma 1 73.8 73.8 73.8 10

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