biostudies-literatureShao LCentral South UniversityChangsha Association for Science and Technology32https://www.ebi.ac.uk/biostudies/studies/S-EPMC12831273biostudies-literatureUnknown26(1)Approximately 5-10% of all cancer types are hereditary cancer syndromes, which are caused by pathogenic mutations in cancer susceptibility genes. In this investigation, a hereditary cancer pedigree was collected from a province in southern China, and the proband was a 31-year-old woman with breast cancer. Utilizing blood whole exome sequencing technology and bioinformatics analysis, the sole heterozygous missense mutation in PIBF1 that exhibits trait segregation was identified: PIBF1 (p.R405Q). The pedigree also included two other mutations that may be linked to carcinogenesis: RAD51D (p.K91Ifs*13) and BRCA2 (p.G3134Afs*29). This research concentrated on PIBF1 (p.R405Q) and employed breast cancer as a tumor model. In vitro and in vivo experiments showed that PIBF1-WT suppressed breast cancCancer cell internationalPIBF1 (p.R405Q) germline variant identified in cancer susceptibility family impairs protein stability and function.PMC128312732024ZZTS0509No. AY-2024-01-023Liu XWu JYu RWen LShao LXu QWang YZhang SZhao JfalsePIBF1 (p.R405Q) germline variant identified in cancer susceptibility family impairs protein stability and function.Approximately 5-10% of all cancer types are hereditary cancer syndromes, which are caused by pathogenic mutations in cancer susceptibility genes. In this investigation, a hereditary cancer pedigree was collected from a province in southern China, and the proband was a 31-year-old woman with breast cancer. Utilizing blood whole exome sequencing technology and bioinformatics analysis, the sole heterozygous missense mutation in PIBF1 that exhibits trait segregation was identified: PIBF1 (p.R405Q). The pedigree also included two other mutations that may be linked to carcinogenesis: RAD51D (p.K91Ifs*13) and BRCA2 (p.G3134Afs*29). This research concentrated on PIBF1 (p.R405Q) and employed breast cancer as a tumor model. In vitro and in vivo experiments showed that PIBF1-WT suppressed breast canc2025-01-01T00:00:00Z2025 Dec2026-06-21T03:11:34.694Z2026-06-21T03:07:39.254ZS-EPMC128312734141986810.1186/s12935-025-04132-y