BRCA1 status in Pakistani breast cancer patients with moderate family history

To determine BRCA1 status in breast carcinoma patients of Pakistani origin. Observational study. The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009. Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative [mother, daughter, sister] diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism [SSCP] assay while protein truncation test [PTT] was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing. Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years [range 24-65 years]. Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 [c.271T > G], exon 20 [c.5231 delG] and exon 11 [c.1123 T > G] were reported first time in the Pakistani population. Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent

Medullary carcinoma of breast with a novel germline mutation 1123T>G in exon11 of brca1

Breast cancer, the most common malignancy in females, has an estimated 5-10% hereditary predisposition. BRCA1 is a tumor suppressor gene and is known to be responsible for breast cancer and breast-ovarian cancers running in families. In breast caner patients, several mutations in BRCA1 have been reported throughout the gene. This report describes identification of a mutation in BRCA1 gene using protein truncation [PTT] assay in a patient with medullary carcinoma of breast who also had a family history of breast cancer. Following DNA sequencing, the mutation was confirmed as substitution of thymine at position 1123 with guanine of exon 11 [1123 T>G]. This mutation can be added to the pool of known BRCA1 mutations in Pakistani population, which will help in developing a local screening panel of BRCA1 mutations