A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer

We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH.We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1 locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes.This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.Breast cancer is the most common cancer among women, excluding non-melanoma skin cancers, and constitutes, after lung cancer, the second leading cause of cancer deaths in women. According to the American Cancer Society, about 1.3 million women will be diagnosed with breast cancer annually worldwide, and about 465,000 will die from this disease [1]. About 5-10% of all breast cancers are estimated to be hereditary, and germline mutations in the tumor-suppressor genes BRCA1 (MIM#113705) and BRCA2 (MIM#600185) are found in a proportion of this group [2,3]. Family history of breast and ovarian cancer, besides breast cancer bilaterality, early-onset breast cancer and ethnicity, constitute the basic criteria for identifying cases affected by BRCA1 or BRCA2 mutations. However, a negative family history does not exclude the presence of a germline mutation in these genes; in fact, in unselected populations, the estimated prevalence of BRCA1 mutations in medullary and triple negative breast cancers is about 18% before age 50 [4-8].Most of the reported BRCA1 and BRCA2 mutations are characterized by deletions, insertions, nonsense mutations and splice variants that result in a truncated protein. Nevertheless, an increasin