A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome

AbstractScreening tumor susceptibility genes helps in identifying powerful biomarkers for hereditary cancer monitoring, prevention, and diagnosis, providing opportunities for understanding potential molecular mechanisms and biomarkers for the precise treatment of hereditary cancer syndromes. Whole-exome sequencing of blood and bioinformatics analysis uncovered a novel RBBP8(p.E281*) germline mutation in a family with hereditary cancer syndrome, which was verified by Sanger sequencing. Cell proliferation, colony formation, cell migration, and in vivo tumorigenesis were investigated by CCK8, colony formation, Transwell, and in vivo xenograft assays. Protein localization and interaction were detected by immunofluorescence, nuclear and cytoplasmic protein extraction kits, and Co-IP. A new heterozygous germline mutation of the RBBP8(p.E281*) gene was found to be associated with familial hereditary cancer syndrome. RBBP8-WT was mainly detected in the nucleus and interacts with BRCA1. In contrast, RBBP8(p.E281*) is mainly located in the cytoplasm, with no interaction with BRCA1. RBBP8(p.E281*) variant plays an oncogenic role in the cytoplasm in addition to its loss of function in the nucleus, which promotes breast cancer proliferation, in vivo tumorigenesis, and migration. Compared with the control group, RBBP8(p.E281*) showed elevated cell death in response to cisplatin and olaparib treatment. A novel RBBP8(p.E281*) germline mutation was identified from familial hereditary cancer s...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research