The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma.

ABSTRACT:

Abstract

Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.4% of patients with an HY karyotype without IgH translocations, challenging acquisition of an HY karyotype as the earliest somatic event. Remarkably, these deletions affected tumor suppressor genes (TSGs) and/or oncogenes in 2.4% of patients with an HY karyotype without IgH translocations, supporting their role in MM pathogenesis. Furthermore, our study points

SUBMITTER: Cirrincione AM 

PROVIDER: S-EPMC11375460 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature