Germline copy number variations and cancer predisposition

Author(s)

Victorino Krepischi, Ana Cristina ^{[1, 2]} ; Pearson, Peter Lees ^[3] ; Rosenberg, Carla ^[3]

Affiliation

^[1] AC Camargo Hosp, CIPE, Sao Paulo - Brazil

^[2] Nat Inst Sci & Technol Oncogen, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Sao Paulo - Brazil

• Document type: Review article
• Source: FUTURE ONCOLOGY; v. 8, n. 4, p. 441-450, APR 2012.
• Web of Science Citations: 40

Abstract

We present an overview of the role of germline copy number variations (CNVs) in cancer predisposition. CNVs represent a significant source of genetic diversity, although the mechanisms by which they influence cancer susceptibility still remain largely unknown. Approximately 100 highly penetrant germline mutant genes are now known to cause cancer predisposition inherited in a Mendelian fashion; in this review, we show that nearly half of these genes have also been observed as rare CNVs associated with cancer. However, these highly penetrant alleles seem to account for less than 5% of all familial cancers. We surmise that most of the genetic risk of cancer in the general population must largely involve genes of low or moderate penetrance. In the last 5 years, studies have demonstrated that although common low penetrant CNVs are modest contributors to cancer individually, their combined impact on cancer predisposition must be taken into account in estimating cancer risk. (AU)

• FAPESP's process: 09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes
• Grantee: Carla Rosenberg
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants