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| Author(s): |
Karina Augusto Escobar
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2011-08-08 |
| Examining board members: |
Miriam Hatsue Honda Federico;
Maria Lucia Hirata Katayama;
Benedito Mauro Rossi
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| Advisor: | Miriam Hatsue Honda Federico |
| Abstract | |
Introduction: Mutation in BRCA1 and BRCA2 genes are responsible for more than 50% of hereditarian breast and ovarian cancer cases. Nowadays, we still dont know the Brazilian mutation profile for these genes, except when founder mutations occur in specific ethnic groups. Objetives: Detection of mutation and polymorphisms in BRCA1 and BRCA2 genes in 73 breast cancer patients selected for genetic testing. Casuistic and methods: we have realized direct sequencing of BRCA1 and BRCA2 in 73 patients, whose 63 have had breast cancer and showed at least 10% of risk according to Frank, Evans and BRCAPRO, two patients with ovarian cancer and eight healthy individuals of strong family history of cancer linked to mutations in BRCA1 and BRCA2. Results: We have found 60 mutations in BRCA1: 13 missense mutations (including the deleterious R71G), seven synonymous mutations, one frameshift mutation (the deleterious 5382insC), one nonsense mutation (the deleterious R1751X), one in-frame deletion, one 3UTR mutation and 36 intronic variants. In BRCA2 we have found 57 mutations: 26 missense mutations, one 5UTR mutation, 11 synonymous mutations, 14 intronic variants, two nonsense mutations (the deleterious R2318X and R3128X) and three frameshift mutations (5844del5, 6610insTT and 6633del5). No mutation was detected by MLPA technique. Discussion and final considerations: Nine of 73 studied individuals carry deleterious mutations. Among them, the Ashkenazi founder mutation 5382insC has been found in two unrelated patients and it was previously reported by another research group for its high prevalence on a population from São Paulo. Alterations of unknown clinical significance have been found all over BRCA1 and BRCA2 gene extension and are countless. Some of them are shown only in one patient, leading us to think that maybe one or a few might have a pathogenic effect, like 6610insTT, which leads to a BRCA2 incomplete protein and was shown in 3 generations of a family. MLPA technique have not detected large genomic rearrangements in both genes, showing that this kind of mutation is not frequent on our cohort and maybe this genetic alteration characterizes less miscigenated populations. So, we emphasize the importance of enlarge this study and stimulate future researches, aiming an efficient genetic counseling, decreasing inconclusive cases generated by unknown clinical significance variants, and follow up of affected families (AU) | |