Analysis of Reciprocal Pair Rearrangements Found Among Homologous Recombination Deficient Tumors

Researchers have uncovered what appear to be a class of DNA rearrangements that are specific to BRCA1 or BRCA2 deficiencies. A team from New York University and elsewhere conducted a graph genome analysis of short-read genome sequencing profiles of primary cancers associated with homologous recombination deficiency, including tumors with BRCA1 or BRCA2 alterations as well as ones that were homologous recombination proficient. As they report in Nature, the researchers found reciprocal pair rearrangements among the homologous recombination-deficient tumors. These rearrangements could, they add, lead to two different chromosomal outcomes — one in cis and one in trans — which the researchers said likely stemmed from the effects of two other repair processes. "The long molecules tell us that these scars come from two backup repair mechanisms — homology-independent replication restart and single-strand annealing — that may keep HR-deficient cancer cells alive," co- senior author Marcin Imieliński, director of cancer genomics at NYU's Perlmutter Cancer Center, says in a statement. "Blocking the mechanisms may represent new ways to treat these cancers."