TY - JOUR
T1 - Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays
AU - Coombs, Catherine C.
AU - Gillis, Nancy K.
AU - Tan, Xianming
AU - Berg, Jonathan S.
AU - Ball, Markus
AU - Balasis, Maria E.
AU - Montgomery, Nathan D.
AU - Bolton, Kelly L.
AU - Parker, Joel S.
AU - Mesa, Tania E.
AU - Yoder, Sean J.
AU - Hayward, Michele C.
AU - Patel, Nirali M.
AU - Richards, Kristy L.
AU - Walko, Christine M.
AU - Knepper, Todd C.
AU - Soper, John T.
AU - Weiss, Jared
AU - Grilley-Olson, Juneko E.
AU - Kim, William Y.
AU - Shelton Earp, H.
AU - Levine, Ross L.
AU - Papaemmanuil, Elli
AU - Zehir, Ahmet
AU - Neil Hayes, D.
AU - Padron, Eric
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056321419&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-1201
DO - 10.1158/1078-0432.CCR-18-1201
M3 - Article
C2 - 29866652
AN - SCOPUS:85056321419
SN - 1078-0432
VL - 24
SP - 5918
EP - 5924
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -