Skip NavigationSkip to Content
Return Return to Search Results

Comprehensive analysis of CDKN2A (p16(INK4A)/p14(ARF)) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma

  1. Author:
    Laud, K.
    Marian, C.
    Avril, M. F.
    Barrois, M.
    Chompret, A.
    Goldstein, A. M.
    Tucker, M. A.
    Clark, P. A.
    Peters, G.
    Chaudru, V.
    Demenais, F.
    Spatz, A.
    Smith, M. W.
    Lenoir, G. M.
    Bressac-de Paillerets, B.
    French Hereditary Melanoma Study, G.

  2. Author Address

    Inst Gustave Roussy, Serv Genet, F-94800 Villejuif, France. Inst Gustave Roussy, Dept Med, F-94800 Villejuif, France. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Lincolns Inn Fields Labs, Canc Res UK, London Res Inst, London WC2A 3PX, England. Univ Evry, INSERM, F-91034 Evry, France. Inst Gustave Roussy, Serv Anatomopathol, F-94800 Villejuif, France. NCI, Lab Genom Divers, Ctr Canc Res, SAIC Frederick,NIH,DHHS, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick,NIH,DHHS, Frederick, MD 21702 USA.;Bressac-de Paillerets, B, Inst Gustave Roussy, Serv Genet, 39 Rue Camille Desmoulins, F-94805 Villejuif, France.;bressac@igr.fr
    1. Year: 2006
    2. Date: Jan
  2. Journal: Journal of Medical Genetics
    1. 43
    2. 1
    3. Pages: 39-47
  4. Type of Article: Article
  5. ISSN: 0022-2593
  1. Abstract:

    Objective: Comprehensive analysis of the 9p21 locus including the CDKN2A, ARF, and CDKN2B genes in 53 individuals from melanoma index cases considered to be at heightened risk of melanoma. Methods and Results: Using a combination of DNA sequencing, gene copy number by real time quantitative PCR, linkage analysis, and transcript analysis in haploid somatic cell hybrids, we found no evidence for germline alteration in either coding or non- coding domains of CDKN2A and CDKN2B. However, we identified a p14(ARF) exon 1 beta missense germline mutation ( G16D) in a melanoma- neural system tumour syndrome ( CMM+ NST) family and a 8474 bp germline deletion from 196 bp upstream of p14(ARF) exon 1 beta initiation codon to 11233 bp upstream of exon 1 alpha of p16(INK4A) in a family with five melanoma cases. For three out of 10 families with at least three melanoma cases, the disease gene was unlinked to the 9p21 region, while linkage analysis was not fully conclusive for seven families. Conclusions: These data reinforce the hypothesis that ARF is a melanoma susceptibility gene and suggest that germline deletions specifically affecting p14(ARF) may not be solely responsible for NST susceptibility. Predisposition to CMM+ NST could either be due to complete disruption of the CDKN2A locus or be the result of more complex genetic inheritance. In addition, the absence of any genetic alteration in 50 melanoma prone families or patients suggests the presence of additional tumour suppressor genes possibly in the 9p21 region, and on other chromosomes.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1136/jmg.2005.033498
  3. View record in Web of Science®
  4. WOS: 000234406700005

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel