We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Genomic landscape of advanced prostate cancer patients with BRCA1 versus BRCA2 mutations as detected by comprehensive genomic profiling of cell-free DNA.
- Authors
Swami, Umang; Zimmerman, Raquel Mae; Nussenzveig, Roberto H.; Hernandez, Edgar Javier; Yeonjung Jo; Sayegh, Nicolas; Wesolowski, Sergiusz; Kiedrowski, Lesli A.; Barata, Pedro C.; Lemmon, Gordon Howard; Bilen, Mehmet A.; Heath, Elisabeth I.; Nandagopal, Lakshminarayan; Babiker, Hani M.; Pal, Sumanta K.; Lilly, Michael; Maughan, Benjamin L.; Haaland, Benjamin; Yandell, Mark; Sartor, Oliver
- Abstract
BRCA1-mutated prostate cancer has been shown to be less responsive to poly (ADP-ribose) polymerase (PARP) inhibitors as compared to BRCA2-mutated prostate cancer. The reason for this differential response is not clear. We hypothesized this differential sensitivity to PARP inhibitors may be explained by distinct genomic landscapes of BRCA1 versus BRCA2 co-segregating genes. In a large dataset of 7,707 men with advanced prostate cancer undergoing comprehensive genomic profiling (CGP) of cell-free DNA (cfDNA), 614 men harbored BRCA1 and/or BRCA2 alterations. Differences in the genomic landscape of co-segregating genes was investigated by Fisher's exact test and probabilistic graphical models (PGMs). Results demonstrated that BRCA1 was significantly associated with six other genes, while BRCA2 was not significantly associated with any gene. These findings suggest BRCA2 may be the main driver mutation, while BRCA1 mutations tend to co-segregate with mutations in other molecular pathways contributing to prostate cancer progression. These hypothesis-generating data may explain the differential response to PARP inhibition and guide towards the development of combinatorial drug regimens in those with BRCA1 mutation.
- Subjects
PROSTATE cancer; PROSTATE cancer patients; CELL-free DNA; BRCA genes; CANCER patients; CIRCULATING tumor DNA; FISHER exact test
- Publication
Frontiers in Oncology, 2022, Vol 12, p1
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2022.966534