Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays Journal Article

Authors: Coombs, C. C.; Gillis, N. K.; Tan, X.; Berg, J. S.; Ball, M.; Balasis, M. E.; Montgomery, N. D.; Bolton, K. L.; Parker, J. S.; Mesa, T. E.; Yoder, S. J.; Hayward, M. C.; Patel, N. M.; Richards, K. L.; Walko, C. M.; Knepper, T. C.; Soper, J. T.; Weiss, J.; Grilley-Olson, J. E.; Kim, W. Y.; Earp, H. S. 3rd; Levine, R. L.; Papaemmanuil, E.; Zehir, A.; Hayes, D. N.; Padron, E.
Article Title: Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays
Abstract: Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care.
Keywords: risk; blood; genomics; variants; ppm1d
Journal Title: Clinical Cancer Research
Volume: 24
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2018-12-01
Start Page: 5918
End Page: 5924
Language: English
ACCESSION: WOS:000452374700016
DOI: 10.1158/1078-0432.Ccr-18-1201
PUBMED: 29866652
Notes: Article -- Source: Wos
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MSK Authors
  1. Ross Levine
    464 Levine
  2. Ahmet Zehir
    145 Zehir
  3. Kelly Leigh Bolton
    3 Bolton