Mutation analysis of the BRCA1 and BRCA2 genes in Turkish patients with breast cancer.
Bildiriler > Özet Bildiri · 2015
Yazarlar: Angela Apessos, Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Konstantinos Agiannitopoulos, Sualp Tansan, Ceyhun Irgil, Erhan GÖKMEN, Metin Cakmakci, Can Basaran, Ajlan Atasoy, Gul Basaran, George Nasioulas
Journal of Clinical Oncology, Amerika Birleşik Devletleri, Uluslararası, Sözlü Sunum, Özet Bildiri, 2015-2015, Wos, cilt 33, ss e12536-e12536
DOI: 10.1200/jco.2015.33.15_suppl.e12536
Özet
e12536 Background: Approximately 5-10% of breast cancer cases are hereditary. Germline mutations in the BRCA1 and BRCA2genes are responsible for 80% of inherited breast cancer cases. Carriers of such mutations are usually members of families with at least 1-2 cases of breast cancer diagnosed before the age of 40 years. Pathogenic mutations throughout the coding region of the two genes have been identified. Founder mutations have been identified in various populations. AIM: To date there have been limited data on the contribution of mutations in the BRCA1 and BRCA2genes in Turkish families with breast cancer. We aimed to identify mutations in high risk patients of this population, as judged by the age at diagnosis of breast cancer and the immunohistochemical characterisistcs of the patients’ tumours. Methods: In the past 2 years, 114 families have been analyzed by our group. Genomic DNA extracted from blood samples was subjected to PCR using the commercially available CE IVD BRCA MASTR Dx kit (MULTIPLICOM NV, J Mol Diag, 14:623-30, 2012) for the two genes. Sequencing was carried out using the Next Generation Sequencing platform MiSeq (Illumina). Large genomic rearrangements, in addition to the presence of the 1100delC mutation in the CHEK2 gene, were investigated by MLPA (BRCA1: P002, BRCA2, CHEK2:P045, MRC Holland; AJHG 67:841-50, 2000). Results: A pathogenic mutation has been identified in 16 (14%) of the 114 patients analyzed. Of the mutations identified, 7 were located in the BRCA1 gene and 9 in BRCA2. Of the mutations identified 5 (1 in BRCA1 and 4 in BRCA2) have not been previously described. Most interestingly, 7 of the mutations (4 in BRCA1 and 3 in BRCA2) were large genomic rearrangements, encompassing one or more exons of the gene. Finally, 15 variants which have not been previously described were identified. Conclusions: Our results indicate that in accordance to the frequency of mutations identified in other populations, pathogenic mutations in the BRCA1 and BRCA2 genes can be identified in 14% of high risk Turkish families. Of those, a striking 44% are large genomic rearrangements, indicating that analysis of these two genes in patients of Turkish origin must consist of a variety of methods, capable of detecting all types of mutations.