Abstract 4916: Co-occurring clonal hematopoiesis in UK Biobank participants with prior cancer

作者：Kara M. Barnao, Aubrey K. Hubbard, Irenaeus C.C. Chan, Weiyin Zhou, Corey D. Young, Rebecca L. Kelly, Derek W. Brown, Giulio Genovese, Duc Tran, Yin Cao, Stephen J. Chanock, Kelly L. Bolton, Mitchell J. Machiela · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-4916 · 被引用次数：1 · 研究领域：Cancer Genomics and Diagnostics、Acute Myeloid Leukemia Research、Lymphoma Diagnosis and Treatment

Abstract Clonal hematopoiesis (CH) describes the age-related clonal expansion of hematopoietic stem cells, driven by either acquired mutations in driver genes (referred to as clonal hematopoiesis of indeterminate potential (CHIP)), or by large-scale mosaic chromosomal alterations (mCAs). Evidence from previous studies indicate anti-cancer agents, such as chemotherapy and radiation therapy, may promote the expansion of clones with DNA damage response mutations (e.g., TP53, PPM1D, and CHEK2). However, the co-occurrence of CHIP and mCAs in participants with prior cancer has not been extensively characterized. We therefore examined the frequency of co-occurring CHIP and mCAs to further evaluate the landscape of CH within individuals with prior cancer diagnoses. We analyzed sequencing and genotyping array data from 34, 339 UK Biobank participants with a prior cancer diagnosis. Among these, 2, 756 CHIP events were detected in 2, 470 (7.2%) of participants, at a frequency 1.5 times greater than those participants with no prior cancer diagnosis (N = 453, 807). TP53, PPM1D, MYD88, ATM, JAK2, and CALR CHIP mutations in particular were detected at increased rates in those with prior cancer (ORs ranging from 1.9 for TP53 mutations to 6.1 for CALR mutations, p < 6.5 × 10-4). Autosomal mCAs were also detected at a higher rate compared to those with no prior cancer diagnoses; 2, 100 events were detected in 1, 665 participants (4.8% vs 3.0% in cancer-free participants). Specifically, ...