Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers.

ABSTRACT: Homologous recombination (HR) deficiency is associated with DNA rearrangements and cytogenetic aberrations¹. Paradoxically, the types of DNA rearrangements that are specifically associated with HR-deficient cancers only minimally affect chromosomal structure². Here, to address this apparent contradiction, we combined genome-graph analysis of short-read whole-genome sequencing (WGS) profiles across thousands of tumours with deep linked-read WGS of 46 BRCA1- or BRCA2-mutant breast cancers. These data revealed a distinct class of HR-deficiency-enriched rearrangements called reciprocal pairs. Linked-read WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long-molecule

SUBMITTER: Setton J 

PROVIDER: S-EPMC10482687 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature