For individual HRR pathway genes other than BRCA1/ 2, LOH-positive mutations in gATM, gBRIP1, gFANCM, gPALB2, gRAD51C, sATM, sCDK12, and sFANCD2 had high HRD scores, while mutations at these loci not classified as LOH did not. Mutations with loss of heterozygosity (LOH) were found to be more common and these mutations had higher HRD scores compared with mutations without LOH. The analysis revealed biallelic alterations in HRR genes other than BRCA1/2 that were also associated with elevated genomic scar scores. Researchers analyzed HRR pathway gene alterations and their clinical significance using the data on all solid cancers from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. However, the clinical significance of scar scores and mutations in other homologous recombination repair (HRR)-related genes is unclear. Thus, HRD-associated sensitivity to PARPis and platinum-based therapy is used as a therapeutic biomarker in these cancers. Patients who are carriers of BRCA1/ 2 mutations respond better to platinum-based chemotherapies and PARP inhibitors (PARPis). The researchers noted that, among patients with breast and ovarian cancer, HRD is associated with genomic alterations in BRCA1/ 2 and genomic scar signatures. The research was published in the Journal of Clinical Oncology. A comprehensive pan-cancer analysis of biomarkers of homologous recombination DNA repair deficiency (HRD) showed that the association between biallelic alterations in HRD pathway genes and genomic scar signatures differed significantly by sex and the presence of somatic TP53 mutations.
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