The gene encoding this enzyme, EDH17B2, has been mapped to chromosome 17, region q12-q21, in the vicinity of BRCA1, as as yet unidentified gene that appears to be involved in familial breast cancer and in familial ovarian cancer.
We identified a homozygous deletion in a pancreatic carcinoma (DPC) that localized to a 1-cM region at chromosome 13q12.3, which lay within the 6-cM locus of familial breast cancer susceptibility (BRCA-2).
Analysis of polymorphic loci on 17q in the series of hybrid clones suggested that a tumor suppressor gene associated with prostate cancer was located in a region no more than 28 cM long at 17q12-q22, which includes the BRCA1 gene involved in hereditary breast cancer.
We have studied BRCA1, the breast cancer susceptibility gene, as a determinant of susceptibility to breast cancer by linkage analyses in 11 families, but our results indicate that BRCA1 may not be important for development of familial breast cancer in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer.
The correlation reported previously, as well as our current findings, suggest that further investigations are warranted to understand the possible linkage of the ER gene locus to hereditary breast cancer.
We have investigated the roles of the Rb and the hereditary breast cancer susceptibility gene (BRCA2), which lie within 25 cM of each other on chromosome 13q12-14, in the multi-step aetiology of endocrine tumours.
The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families.
These results suggest that BRCA2 will explain a significant proportion of hereditary breast cancer in the Netherlands, and, together with BRCA1, account for the majority of all high-risk families.
This suggests that mutations in the BRCA1 gene may play a significant role in the tumorigenesis of familial breast cancer but not of sporadic breast cancer.
However, it is not yet clear what proportion of hereditary breast cancer is explained by BRCA1 and BRCA2 or by some other unidentified susceptibility gene(s).
The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers.
Loss of heterozygosity (LOH) was analysed in 84 primary tumours from sporadic, familial and hereditary breast cancer using five microsatellite markers spanning the chromosomal region 13q12-q13 which harbours the BRCA2 breast cancer susceptibility gene, and using one other marker located within the RBI tumour-suppressor gene at 13q14.
Compared with non-HBC, invasive BRCA1-related HBC had a lower diploidy rate (13% vs. 35%; P = 0.002), lower mean aneuploid DNA index (1.53 vs. 1.73; P= 0.002), and strikingly higher proliferation rates (mitotic grade 3; odds ratio [OR]= 4.42; P= 0.001; aneuploid mean S-phase fraction 16.5% vs. 9.3%, P < 0.0001).