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Germline Genomic Copy Number Variation Contribution to Cancer Predisposition

  1. Amanda Gonçalves Silva1,
  2. Tatiane Cristina Rodrigues1,
  3. Peter Lees Pearson1,
  4. Carla Rosenberg1,
  5. Ana Cristina Victorino Krepischi2

Published Online: 20 SEP 2013

DOI: 10.1002/9780470015902.a0025028



How to Cite

Silva, A. G., Rodrigues, T. C., Pearson, P. L., Rosenberg, C. and Krepischi, A. C. V. 2013. Germline Genomic Copy Number Variation Contribution to Cancer Predisposition. eLS. .

Author Information

  1. 1

    Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

  2. 2

    CIPE – A. C. Camargo Cancer Center, São Paulo, Brazil

Publication History

  1. Published Online: 20 SEP 2013



The majority of familial cancer remains with unknown genetic aetiology. Issues impairing the discovery of new genes in complex diseases such as cancer include multifactorial origin, incomplete penetrance of the disease and late-onset. The authors present an outline of the contribution of constitutive deoxyribonucleic acid copy number variations (CNVs) in cancer predisposition. Even though the mechanisms by which germline CNVs influence disease are hitherto largely speculative, nowadays it is consensual that they play a major role in a range of human pathologies. Point mutations have been far more commonly described, mainly because sequencing is the first-tier diagnostic test, but deletions and duplications of known cancer genes have been reported as an alternative mechanism for cancer susceptibility. Additionally, CNV screening in familial cancer cohorts with unknown genetic aetiology has pointed to new candidate genes for high cancer risk. Therefore, this type of genomic variation must be taken into account in the cancer risk assessment.

Key Concepts:

  • Structural variation, including copy number variation (CNV), is responsible for a large fraction of the genetic diversity of the human genome.

  • CNVs can be inherited in a Mendelian fashion or occur de novo.

  • Germline CNVs play an important role in a range of human pathologies through several mechanisms, mainly affecting gene dosage or function.

  • Nearly half of the approximately 100 Mendelian cancer predisposition genes were also reported as rare pathogenic germline CNVs.

  • Next-generation sequencing (NGS) combined with automated high throughput data analysis is the most promising approach for elucidating the contribution of both CNVs and point mutations to cancer predisposition.


  • structural variation;
  • CNV;
  • cancer predisposition;
  • germline alterations;
  • next-generation sequencing