Germline copy number variation and cancer risk

Roland P Kuiper, Marjolijn J L Ligtenberg, Nicoline Hoogerbrugge, Ad Geurts van Kessel

Research output: Contribution to journalReview articlepeer-review


The human genome is subject to substantial structural variation, including copy number variation (CNV). Constitutional CNVs may either represent benign polymorphic variants or be associated with disease, including cancer predisposition. Rare nonpolymorphic CNVs, that is DNA lesions that result in gene deletions, inversions, and/or fusions, may be responsible for a high cancer risk. In addition, we previously elucidated a mechanism by which CNV-based transcriptional read-through mediates inactivation of a neighboring gene through in cis hypermethylation of its promoter. This novel mechanism explains the etiology of a recurrent and strongly inherited tissue-restricted epimutation. Recently, we obtained supporting evidence for such a CNV-associated scenario, suggesting that it may be more prevalent than previously thought. We expect that copy number profiling in unexplained high-risk families will lead to the discovery of additional cancer-predisposing genes and/or mechanisms.

Original languageEnglish
Pages (from-to)282-9
Number of pages8
JournalCurrent opinion in genetics & development
Issue number3
Publication statusPublished - Jun 2010
Externally publishedYes


  • Gene Dosage
  • Genetic Predisposition to Disease/genetics
  • Genome, Human/genetics
  • Germ-Line Mutation/genetics
  • Humans
  • Mutation
  • Neoplasms/genetics
  • Risk Factors


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