Large-Scale Identification of Clonal Hematopoiesis and Mutations Recurrent in Blood Cancers

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations useable for CHIP detection by performing a data mining an...

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Bibliographic Details
Published in:Blood cancer discovery 2021-05, Vol.2 (3), p.226-237
Main Authors: Feusier, Julie E, Arunachalam, Sasi, Tashi, Tsewang, Baker, Monika J, VanSant-Webb, Chad, Ferdig, Amber, Welm, Bryan E, Rodriguez-Flores, Juan L, Ours, Christopher, Jorde, Lynn B, Prchal, Josef T, Mason, Clinton C
Format: Article
Language:English
Subjects:
Adult
Child
Clonal Hematopoiesis
Hematologic Neoplasms - diagnosis
Hematopoiesis - genetics
Humans
Mutation
Neoplasms - diagnosis
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Summary:Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations useable for CHIP detection by performing a data mining analysis of 48 somatic mutation studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with hematologic malignancies. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole exome sequencing data from 4,538 persons belonging to three non-cancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and pre-cancer surveillance for both children and adults.
ISSN:2643-3230
2643-3249
DOI:10.1158/2643-3230.BCD-20-0094