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Large genomic deletions inactivate the BRCA2 gene in breast cancer families

¹ Department of Oncology and Surgical Sciences, Oncology Section, Padua, Italy
² IST-Genova c/o Azienda Ospedaliera, Padua
³ Oncologia Medica, Azienda Ospedaliera, Padua
⁴ Clinica Chirurgica II, Azienda Ospedaliera, Padua

Correspondence to:
Dr Marco Montagna
Department of Oncology and Surgical Sciences, Oncology Section, via Gattamelata 64, I-35128 Padua, Italy; montagna{at}unipd.it] Background: BRCA1 and BRCA2 are the two major genes responsible for the breast and ovarian cancers that cluster in families with a genetically determined predisposition. However, regardless of the mutation detection method employed, the percentage of families without identifiable alterations of these genes exceeds 50%, even when applying stringent criteria for family selection. A small but significant increase in mutation detection rate has resulted from the discovery of large genomic alterations in BRCA1. A few studies have addressed the question of whether BRCA2 might be inactivated by the same kinds of alteration, but most were either done on a relatively small number of samples or employed cumbersome mutation detection methods of variable sensitivity.

Objective: To analyse 121 highly selected families using the recently available BRCA2 multiplex ligation dependent probe amplification (MLPA) technique.

Results: Three different large genomic deletions were identified and confirmed by analysis of the mutant transcript and genomic characterisation of the breakpoints.

Conclusions: Contrary to initial suggestions, the presence of BRCA2 genomic rearrangements is worth investigating in high risk breast or ovarian cancer families.

Abbreviations: DHPLC, denaturing high performance liquid chromatography; HBC/HBOC, hereditary breast/ovarian cancer; MLPA, multiplex ligation dependent probe amplification; SHBC/SHBOC, suspected hereditary breast/ovarian cancer

Keywords: hereditary breast cancer; BRCA2; genomic rearrangement; MLPA

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