Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer

Hereditary Cancer in Clinical Practice

Tirzah Braz Petta Lajus⁵  Mary-Claire King⁴  Tom Walsh⁴  Lucymara Fassarela Agnez-Lima¹  Carlos Cesar de Oliveira Ramos³  Patricia Cristina Pascoto Moura⁵  Betina Menezes Albuquerque²  Ana Rafaela de Souza Timoteo¹ 

[1] Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Natal, RN, Brazil;Hospital Liga contra o Câncer, Departamento de Mastologia, Natal, RN, Brazil;Hospital Liga contra o Câncer, Laboratório de Patologia Cirúrgica, Natal, RN, Brazil;University of Washington, Department of Medicine and Genome Sciences, Health Sciences K-160, Seattle, USA;Hospital Liga contra o Câncer, Departamento de Pesquisa Translacional, Natal, RN, Brazil

关键词: Large genomic deletion;    Next-generation sequencing;    BRCA2 mutation;    Male Breast Cancer (MBC);   

Others  :  1133775
DOI  :  10.1186/s13053-014-0022-x

 received in 2014-09-02, accepted in 2014-12-15,  发布年份 2015

【 摘 要 】

Background

Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer.

Methods and results

The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496.

Conclusion

Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

【 授权许可】

   
2015 Timoteo et al.; licensee BioMed Central.

【 图 表 】

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