Landscape of BRIP1 molecular lesions in gastrointestinal cancers from published genomic studies

BACKGROUND: BRIP1 is a helicase that partners with BRCA1 in the homologous recombination (HR) step in the repair of DNA inter-strand cross-link lesions. It is a rare cause of hereditary ovarian cancer in patients with no mutations of BRCA1 or BRCA2. The role of the protein in other cancers such as gastrointestinal (GI) carcinomas is less well characterized but given its role in DNA repair it could be a candidate tumor suppressor similarly to the two BRCA proteins. AIM: To analyze the role of helicase BRIP1 (FANCJ) in GI cancers pathogenesis. METHODS: Publicly available data from genomic studies of esophageal, gastric, pancreatic, cholangiocarcinomas and colorectal cancers were interrogated to unveil the role of BRIP1 in these carcinomas and to discover associations of lesions in BRIP1 with other more common molecular defects in these cancers. RESULTS: Molecular lesions in BRIP1 were rare (3.6% of all samples) in GI cancers and consisted almost exclusively of mutations and amplifications. Among mutations, 40% were possibly pathogenic according to the OncoKB database. A majority of BRIP1 mutated GI cancers were hyper-mutated due to concomitant mutations in mismatch repair or polymerase ε and δ1 genes. No associations were discovered between amplifications of BRIP1 and any mutated genes. In gastroesophageal cancers BRIP1 amplification commonly co-occurs with ERBB2 amplification. CONCLUSION: Overall BRIP1 molecular defects do not seem to play a major role in GI cancers whereas mutations frequently occur in hypermutated carcinomas and co-occur with other HR genes mutations. Despite their rarity, BRIP1 defects may present an opportunity for therapeutic interventions similar to other HR defects.