https://www.selleckchem.com/products/e-64.html The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.Seventeen years of archaeological and anthropological expeditions in North-Eastern Siberia (in the Sakha Republic, Yakutia) have permitted the genetic analysis of 150 ancient (15th-19th century) and 510 modern individuals. Almost all males were successfully analysed (Y-STR) and this allowed us to identify paternal lineages and their geographical expansion through time. This genetic data was confronted with mythological, historical and material evidence to establish the sequence of events that built the modern Yakut genetic diversity. We show that the ancient Yakuts recovered from this large collection of graves are not representative of an ancient population. Uncommonly, we were also able to demonstrate that the funerary preference observed here involved three specific male lineages, especially in the 18th century. Moreover,