Identification of a novel germline BRCA2 variant in a male with breast cancer / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a male with breast cancer and a sister who had deceased of the disease.@*METHODS@#Medical and family history of the proband was collected. Next-generation sequencing was carried out to detect potential variant associated with breast cancer, and Sanger sequencing was used to verify the result.@*RESULTS@#The proband was found to harbor a novel heterozygous c.6018dupT variant of the BRCA2 gene which may cause premature termination of mRNA translation, resulting in a truncated protein. Combined with the family history, the variant was deduced to be a germline mutation. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.6018dupT variant of BRCA2 gene was predicted to be pathogenic (PVS1+PM1/2+PP4).@*CONCLUSION@#The germline variant of the BRCA2 gene probably underlay the breast cancer in this pedigree.

Câncer de mama em homem: relato de caso e revisão da literatura / Male breast cancer: a case report and review of the literature

O câncer de mama em homens é uma patologia relativamente incomum. Atinge um homem para cada 1.000 mulheres, representa menos de 1 por cento de todos os cânceres em homens e é responsável por 0,1 por cento da mortalidade por câncer no sexo masculino. Como nas mulheres, o subtipo mais comum é o ductal infiltrativo. No presente trabalho é relatado o caso de um paciente masculino, 67 anos, com nódulo em mama direita com diagnóstico de carcinoma ductal sólido. Apesar de ser incomum, alguns estudos vêm demonstrando um aumento na incidência desses tumores. O exame físico talvez seja a principal ferramenta para o diagnóstico desse tumor. Contudo, a confirmação histopatológica é necessária para avaliação definitiva. Devido à raridade da doença, muitas das atuais modalidades de tratamento são baseadas na experiência com câncer de mama feminino. Este caso evidencia a relevância da conscientização da população sobre essa patologia e ao profissional da saúde em considerar este diagnóstico possível.

Male breast cancer is a fairly uncommon disorder. Affecting only one for a thousand women, it represents less than 1 percent of all male cancers and accounts for 0.1 percent of the male cancer mortality. Just like in women, the most common subtype is the infiltrative ductal. Here we report the case of a 67-year-old male patient with a nodule in the right breast with a diagnosis of solid ductal carcinoma. Although uncommon, a few studies show an increase in the incidence of this tumor. However, histopathologic confirmation is necessary for a definite evaluation. Due to the rarity of the disease, many of the current treatment modalities are based on the experience with female cancer. This case highlights the relevance of raising the awareness of the disease among the general population and health professionals in considering this a potential diagnosis.

Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil

Of all malignant neoplasias affecting women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to determine the frequency of genetic modifications in families with medium and high risk for breast and ovarian cancer from different regions of Brazil. An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high-risk families for breast and/or ovarian cancer. After heredogram construction, a blood sample was taken and DNA extraction was performed in all index cases. The protein truncation test was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Of the 612 individuals submitted to genetic testing, 21 (3.4 percent), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. Of the 19 BRCA1 mutations found in the 18 participants, 7 consisted of ins6kb mutations, 4 were 5382insC, 3 were 2156delGinsCC, 2 were 185delAG, 1 was C1201G, 1 was C3522T, and 1 was 3450del4. With respect to the BRCA2 gene, 3 mutations were found: 5878del10, 5036delA and 4232insA (one case each). The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies on high-risk Brazilian populations. The inclusion of individuals with medium risk may have contributed to the lower prevalence observed.

Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families

BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17 % of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.