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PMID: 19566914 Published · epublish English Journal Article

Copy number variations and cancer.

Genome medicine ·Vol. 1 ·No. 6 ·2009-06-16 ·Pages 62

Shlien A, Malkin D

Abstract

DNA copy number variations (CNVs) are an important component of genetic variation, affecting a greater fraction of the genome than single nucleotide polymorphisms (SNPs). The advent of high-resolution SNP arrays has made it possible to identify CNVs. Characterization of widespread constitutional (germline) CNVs has provided insight into their role in susceptibility to a wide spectrum of diseases, and somatic CNVs can be used to identify regions of the genome involved in disease phenotypes. The role of CNVs as risk factors for cancer is currently underappreciated. However, the genomic instability and structural dynamism that characterize cancer cells would seem to make this form of genetic variation particularly intriguing to study in cancer. Here, we provide a detailed overview of the current understanding of the CNVs that arise in the human genome and explore the emerging literature that reveals associations of both constitutional and somatic CNVs with a wide variety of human cancers.

Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shlien Adam
Departments of Genetics and Genome Biology and Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8.
Malkin David
References (69)
69 references, click to expand
  1. Integrated detection and population-genetic analysis of SNPs and copy number variation.
    Nat Genet. 2008 Oct;40(10):1166-74 PMID: 18776908
  2. A census of human cancer genes.
    Nat Rev Cancer. 2004 Mar;4(3):177-83 PMID: 14993899
  3. Genomic rearrangements of hMSH6 contribute to the genetic predisposition in suspected hereditary non-polyposis colorectal cancer syndrome.
    J Med Genet. 2003 Aug;40(8):597-600 PMID: 12920072
  4. Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families.
    Hum Mol Genet. 2003 May 1;12(9):1055-61 PMID: 12700174
  5. Large-scale copy number polymorphism in the human genome.
    Science. 2004 Jul 23;305(5683):525-8 PMID: 15273396
  6. Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.
    J Med Genet. 1993 May;30(5):369-75 PMID: 8391580
  7. The Catalogue of Somatic Mutations in Cancer (COSMIC).
    Curr Protoc Hum Genet. 2008 Apr;Chapter 10:Unit 10.11 PMID: 18428421
  8. The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.
    Br J Cancer. 2008 Jul 22;99(2):364-70 PMID: 18612309
  9. Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.
    Dev Disabil Res Rev. 2008;14(1):26-34 PMID: 18636634
  10. Large deletions of the PRKAR1A gene in Carney complex.
    Clin Cancer Res. 2008 Jan 15;14(2):388-95 PMID: 18223213
  11. Smith-Magenis syndrome.
    Eur J Hum Genet. 2008 Apr;16(4):412-21 PMID: 18231123
  12. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients.
    Nat Genet. 1997 Nov;17(3):341-5 PMID: 9354803
  13. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification.
    Nucleic Acids Res. 2002 Jun 15;30(12):e57 PMID: 12060695
  14. An Alu-mediated partial SDHC deletion causes familial and sporadic paraganglioma.
    J Med Genet. 2004 Sep;41(9):703-9 PMID: 15342702
  15. Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour.
    Nat Rev Neurosci. 2006 May;7(5):380-93 PMID: 16760918
  16. Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study.
    Hum Mutat. 2005 Feb;25(2):142-9 PMID: 15643609
  17. Deletion of RB exons 24 and 25 causes low-penetrance retinoblastoma.
    Am J Hum Genet. 1997 Sep;61(3):556-70 PMID: 9326321
  18. Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families.
    J Med Genet. 2008 Aug;45(8):535-8 PMID: 18511570
  19. Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes.
    Am J Hum Genet. 2006 Aug;79(2):332-41 PMID: 16826523
  20. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology.
    Expert Rev Mol Med. 2005 Jul 25;7(14):1-20 PMID: 16038620
  21. Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1.
    J Med Genet. 2009 Jan;46(1):68-72 PMID: 19124645
  22. Structural variation in the human genome.
    Nat Rev Genet. 2006 Feb;7(2):85-97 PMID: 16418744
  23. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.
    Nature. 2007 Apr 12;446(7137):758-64 PMID: 17344859
  24. Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot?
    Genes Chromosomes Cancer. 2006 Mar;45(3):213-9 PMID: 16258955
  25. Copy number variant in the candidate tumor suppressor gene MTUS1 and familial breast cancer risk.
    Carcinogenesis. 2007 Jul;28(7):1442-5 PMID: 17301065
  26. Genomic rearrangements of the APC tumor-suppressor gene in familial adenomatous polyposis.
    Hum Genet. 2000 Jan;106(1):101-7 PMID: 10982189
  27. Complete germline deletion of the STK11 gene in a family with Peutz-Jeghers syndrome.
    Eur J Hum Genet. 2004 May;12(5):415-8 PMID: 14970844
  28. Genetic association analysis of copy-number variation (CNV) in human disease pathogenesis.
    Genomics. 2009 Jan;93(1):22-6 PMID: 18822366
  29. Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis.
    J Med Genet. 2005 Feb;42(2):185-92 PMID: 15689459
  30. High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor.
    Hum Genet. 2007 Sep;122(2):117-27 PMID: 17541642
  31. Molecular mechanisms for genomic disorders.
    Annu Rev Genomics Hum Genet. 2002;3:199-242 PMID: 12142364
  32. The contribution of germline rearrangements to the spectrum of BRCA2 mutations.
    J Med Genet. 2006 Sep;43(9):e49 PMID: 16950820
  33. A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.
    J Med Genet. 2006 Nov;43(11):863-6 PMID: 17085682
  34. Relative impact of nucleotide and copy number variation on gene expression phenotypes.
    Science. 2007 Feb 9;315(5813):848-53 PMID: 17289997
  35. Human MHC architecture and evolution: implications for disease association studies.
    Int J Immunogenet. 2008 Jun;35(3):179-92 PMID: 18397301
  36. Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects.
    Am J Med Genet B Neuropsychiatr Genet. 2003 Nov 15;123B(1):39-49 PMID: 14582144
  37. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).
    Nat Genet. 2009 May;41(5):579-84 PMID: 19330030
  38. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.
    Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11264-9 PMID: 18685109
  39. CancerGenes: a gene selection resource for cancer genome projects.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D721-6 PMID: 17088289
  40. A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1.
    Jpn J Cancer Res. 1998 Jan;89(1):1-5 PMID: 9510467
  41. The fine-scale and complex architecture of human copy-number variation.
    Am J Hum Genet. 2008 Mar;82(3):685-95 PMID: 18304495
  42. Germline rates of de novo meiotic deletions and duplications causing several genomic disorders.
    Nat Genet. 2008 Jan;40(1):90-5 PMID: 18059269
  43. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes.
    Am J Hum Genet. 2006 Jun;78(6):1066-74 PMID: 16685657
  44. Segmental copy number variation shapes tissue transcriptomes.
    Nat Genet. 2009 Apr;41(4):424-9 PMID: 19270705
  45. A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population.
    Oncogene. 2001 May 24;20(23):2976-81 PMID: 11420710
  46. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  47. Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma.
    J Clin Endocrinol Metab. 2004 Nov;89(11):5694-9 PMID: 15531530
  48. Detection of large-scale variation in the human genome.
    Nat Genet. 2004 Sep;36(9):949-51 PMID: 15286789
  49. Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
    Nature. 2008 Oct 23;455(7216):1061-8 PMID: 18772890
  50. Copy-number variation and association studies of human disease.
    Nat Genet. 2007 Jul;39(7 Suppl):S37-42 PMID: 17597780
  51. Characterizing the cancer genome in lung adenocarcinoma.
    Nature. 2007 Dec 6;450(7171):893-8 PMID: 17982442
  52. Highly penetrant hereditary cancer syndromes.
    Oncogene. 2004 Aug 23;23(38):6445-70 PMID: 15322516
  53. A large novel deletion in the APC promoter region causes gene silencing and leads to classical familial adenomatous polyposis in a Manitoba Mennonite kindred.
    Hum Genet. 2008 Dec;124(5):535-41 PMID: 18982352
  54. Personal genomes: The case of the missing heritability.
    Nature. 2008 Nov 6;456(7218):18-21 PMID: 18987709
  55. Long-range control of gene expression: emerging mechanisms and disruption in disease.
    Am J Hum Genet. 2005 Jan;76(1):8-32 PMID: 15549674
  56. Screening for TP53 rearrangements in families with the Li-Fraumeni syndrome reveals a complete deletion of the TP53 gene.
    Oncogene. 2003 Feb 13;22(6):840-6 PMID: 12584563
  57. NF1 microdeletion syndrome: refined FISH characterization of sporadic and familial deletions with locus-specific probes.
    Am J Hum Genet. 2000 Jan;66(1):100-9 PMID: 10631140
  58. Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2.
    J Med Genet. 2004 Jul;41(7):529-34 PMID: 15235024
  59. Distribution and functional impact of DNA copy number variation in the rat.
    Nat Genet. 2008 May;40(5):538-45 PMID: 18443591
  60. A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland.
    Breast Cancer Res Treat. 2007 Mar;102(1):119-22 PMID: 16897426
  61. Evidence for WT1 as a Wilms tumor (WT) gene: intragenic germinal deletion in bilateral WT.
    Am J Hum Genet. 1991 May;48(5):997-1003 PMID: 1673293
  62. Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients.
    Am J Hum Genet. 1996 Aug;59(2):417-22 PMID: 8755929
  63. Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis.
    Gut. 2008 May;57(5):623-7 PMID: 18178612
  64. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations.
    Hum Genet. 2007 May;121(3-4):389-400 PMID: 17287951
  65. Germline novel MSH2 deletions and a founder MSH2 deletion associated with anticipation effects in HNPCC.
    Clin Genet. 2007 Feb;71(2):130-9 PMID: 17250661
  66. Global variation in copy number in the human genome.
    Nature. 2006 Nov 23;444(7118):444-54 PMID: 17122850
  67. Mapping the Von Hippel-Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis.
    Hum Mol Genet. 1993 Jul;2(7):879-82 PMID: 8364570
  68. Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma.
    N Engl J Med. 2006 Jun 22;354(25):2729-31 PMID: 16790714
  69. Founding mutations and Alu-mediated recombination in hereditary colon cancer.
    Nat Med. 1995 Nov;1(11):1203-6 PMID: 7584997
Article Info
Journal
Genome medicine
Abbr.
Genome Med
ISSN
1756-994X
DOI
10.1186/gm62
Published
2009-06-16
Epub
2009-00-16
Pages
62
Language
English
Region
England
NLM ID
101475844
PMCID
PMC2703871
External Links
PubMed source DOI: 10.1186/gm62 PMC Full Text View journal details
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