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Germline DNA copy number variation in familial and early-onset breast cancer

Ana CV Krepischi12*, Maria Isabel W Achatz12, Erika MM Santos1, Silvia S Costa3, Bianca CG Lisboa1, Helena Brentani4, Tiago M Santos, Amanda Gonçalves1, Amanda F Nóbrega1, Peter L Pearson3, Angela M Vianna-Morgante3, Dirce M Carraro12, Ricardo R Brentani12 and Carla Rosenberg3

Author Affiliations

1 National Institute of Science and Technology in Oncogenomics, AC Camargo Hospital, Rua Taguá 440, 01508-010, São Paulo, Brazil

2 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090, São Paulo, Brazil

3 Department of Psychiatry, Medicine College, University of São Paulo, Rua Dr Ovídio Pires de Campos 785, 01060-970, São Paulo, Brazil

4 Institute of Mathematics and Statistics, University of São Paulo, Rua do Matão 1010, 05508-090, São Paulo, Brazil

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Breast Cancer Research 2012, 14:R24  doi:10.1186/bcr3109

Published: 7 February 2012



Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease."


Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations.


The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer.


This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples.