BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients.

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population.

Yazici H ，Bitisik O ，Akisik E ，Cabioglu N ，Saip P ，Muslumanoglu M ，Glendon G ，Bengisu E ，Ozbilen S ，Dincer M ，Turkmen S ，Andrulis IL ，Dalay N ，Ozcelik H ... -  《-》

Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224.

Claes K ，Machackova E ，De Vos M ，Mortier G ，De Paepe A ，Messiaen L ... -  《HUMAN MUTATION》

Analysis of breast cancer susceptibility genes BRCA1 and BRCA2 in Thai familial and isolated early-onset breast and ovarian cancer.

Here we report the study on BRCA1 and BRCA2 mutations in 12 Thai breast and/or ovarian cancer families and 6 early-onset breast or breast/ovarian cancer cases without a family history of cancer. Five distinct rare alterations were identified in each gene: four introducing premature stop codons, one in-frame deletion, two missense changes, two intronic alterations and one silent rare variant. The BRCA1 or BRCA2 truncating mutations were detected in four of seven patients with familial or personal history of breast and ovarian cancer, in one of four isolated early onset breast cancer cases and in none of seven breast cancer site specific families. The BRCA1 and BRCA2 mutation yield in Thai patients is consistent with that reported from Europe and North America in similar groups of patients, being particularly high in individuals with personal or family history of breast and ovarian cancer. The BRCA1 and BRCA2 alterations found in this series are different from those identified in other Asian studies, and all but two have never been reported before. We report at least three novel deleterious mutations, the BRCA1 3300delA, BRCA1 744ins20 and BRCA2 6382delT. One in-frame deletion was also found, the BRCA2 5527del9, which seggregated within family members of breast-only cancer patients and was thought to be a cancer-related mutation. BRCA1 3300delA and Asp67Glu alterations were detected each in at least two families and thus could represent founder mutations in Thais.

Patmasiriwat P ，Bhothisuwan K ，Sinilnikova OM ，Chopin S ，Methakijvaroon S ，Badzioch M ，Padungsutt P ，Vattanaviboon P ，Vattanasapt V ，Szabo C ，Saunders GF ，Goldgar D ，Lenoir GM ... -  《-》

Germline mutations in the BRCA1 and BRCA2 genes in Turkish breast/ovarian cancer patients.

In this study we genotyped Turkish breast/ovarian cancer patients for BRCA1/BRCA2 mutations: protein truncation test (PTT) for exon 11 BRCA1 of and, multiplex PCR and denaturing gradient gel electrophoresis (DGGE) for BRCA2, complemented by DNA sequencing. In addition, a modified restriction assay was used for analysis of the predominant Jewish mutations: 185delAG, 5382InsC, Tyr978X (BRCA1) and 6174delT (BRCA2). Eighty three breast/ovarian cancer patients were screened: twenty three had a positive family history of breast/ovarian cancer, ten were males with breast cancer at any age, in eighteen the disease was diagnosed under 40 years of age, one patient had ovarian cancer in addition to breast cancer and one patient had ovarian cancer. All the rest (n=30) were considered sporadic breast cancer cases. Overall, 3 pathogenic mutations (3/53-5.7%) were detected, all in high risk individuals (3/23-13%): a novel (2990insA) and a previously described mutation (R1203X) in BRCA1, and a novel mutation (9255delT) in BRCA2. In addition, three missense mutations [two novel (T42S, N2742S) and a previously published one (S384F)] and two neutral polymorphisms (P9P, P2532P) were detected in BRCA2. Notably none of the male breast cancer patients harbored any mutation, and none of the tested individuals carried any of the Jewish mutations. Our findings suggest that there are no predominant mutations within exon 11 of the BRCA1 and in BRCA2 gene in Turkish high risk families.

Manguoglu AE ，Lüleci G ，Ozçelik T ，Colak T ，Schayek H ，Akaydin M ，Friedman E ... -  《-》

Novel germline BRCA1 and BRCA2 mutations in Turkish women with breast and/or ovarian cancer and their relatives.

Egeli U ，Cecener G ，Tunca B ，Tasdelen I ... -  《CANCER INVESTIGATION》