Novel somatic mutations in the BRCA1 gene in sporadic breast tumors.

Germline mutations in two major susceptibility genes BRCA1 and BRCA2 contribute to the majority of inherited breast and ovarian cancers. Besides the germline mutation, tumor progression depends on the loss of a wild-type allele. Allelic losses in the BRCA1 and BRCA2 loci have also been detected in a high proportion of sporadic breast tumors, suggesting the role of these genes in the development of non-inherited breast cancer. Forty unselected breast tumors were analyzed for the loss of heterozygosity (LOH) at BRCA1 and BRCA2 regions and tumors with allelic deletions were screened for the presence of acquired genetic alterations in respective genes. 21.1% of 38 informative tumor samples carried LOH at the BRCA1 locus whereas 33.3% of 39 informative samples showed LOH at the BRCA2 locus. Pathogenic truncating mutations in the BRCA1 gene were found in two tumor samples with allelic losses, whereas no mutations were identified in the BRCA2 gene. Mutations were not detected in non-tumor samples from the same individuals, which indicated that the BRCA1 allele was inactivated by somatic mutations in tumor tissue. The c.1116G>A (1235G>A) nonsense mutation (p.W372X) belongs to the genetic abnormalities detected infrequently in hereditary tumors; the c.3862delG (3981delG) frameshift mutation (p.E1288fsX1306) is a novel gene alteration. The occurrence of inactivating somatic mutations in sporadic breast tumors suggested the role of the BRCA1 gene in tumorigenesis in at least a minor group of patients with non-familial breast cancer.

Janatova M ，Zikan M ，Dundr P ，Matous B ，Pohlreich P ... -  《-》

BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer.

In order to evaluate the role of BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer, 97 patients with sporadic breast cancer were analyzed for mutations in the BRCA1 and BRCA2 coding regions, by using a combination of fluorescent-conformation sensitive gel electrophoresis (F-CSGE) and direct sequencing. Fifty-five distinct sequence variants were detected, which included three pathogenic truncating mutations, 15 missense mutations, 16 polymorphisms, and 21 intronic variants. Twenty-six of these variants have never been previously reported and may be of Korean-specific origin. Two pathogenic BRCA1 mutations (c.922_924delinsT, c.5445G>A) and one pathogenic BRCA2 mutation (c.2259delT) were observed, and two of these (BRCA1 c.5445G>A and BRCA2 c.2259delT) are novel. The total prevalence of germline pathogenic mutations in BRCA1 and/or BRCA2 in Korean sporadic breast cancer is estimated to be about 3.1%. Considering that the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations in sporadic breast cancer patients. Further study using a larger sample size is required to determine the merits of genetic diagnosis and counseling in breast cancer patients.

Seo JH ，Cho DY ，Ahn SH ，Yoon KS ，Kang CS ，Cho HM ，Lee HS ，Choe JJ ，Choi CW ，Kim BS ，Shin SW ，Kim YH ，Kim JS ，Son GS ，Lee JB ，Koo BH ... -  《-》

BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy.

Ottini L ，Masala G ，D'Amico C ，Mancini B ，Saieva C ，Aceto G ，Gestri D ，Vezzosi V ，Falchetti M ，De Marco M ，Paglierani M ，Cama A ，Bianchi S ，Mariani-Costantini R ，Palli D ... -  《CANCER RESEARCH》

Double heterozygosity for mutations in the BRCA1 and BRCA2 genes in a breast cancer patient.

Tsongalis GJ ，Linfert DR ，Johnson RC ，Ackroyd R ，Berman MM ，Ricci A Jr ... -  《-》

Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India.

Hedau S ，Jain N ，Husain SA ，Mandal AK ，Ray G ，Shahid M ，Kant R ，Gupta V ，Shukla NK ，Deo SS ，Das BC ... -  《BREAST CANCER RESEARCH AND TREATMENT》