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Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2008 by National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: March 20, 2007
Last updated: August 9, 2013
Last verified: April 2008

RATIONALE: Identifying gene mutations and other risk factors in patients with melanoma and in families with a history of hereditary melanoma may help doctors identify persons at risk for melanoma and other types of cancer. It may also help the study of cancer in the future.

PURPOSE: This clinical trial is studying gene mutations in patients with melanoma and in families with a history of hereditary melanoma.

Condition Intervention
Hereditary Multiple Melanoma
Melanoma (Skin)
Genetic: gene expression analysis
Genetic: microarray analysis
Genetic: molecular genetic technique
Genetic: mutation analysis
Other: laboratory biomarker analysis
Procedure: mutation carrier screening
Procedure: study of high risk factors

Study Type: Observational
Official Title: Studies of Familial Melanoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Predictive significance of melanoma susceptibility gene (MSG) mutations in the CDKN2A gene
  • Susceptibility to other types of cancer as a feature of MSG mutations
  • Risk of other types of cancers in mutation carriers
  • Environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers

Estimated Enrollment: 5000
Study Start Date: January 1989
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Detailed Description:


  • Determine the incidence and etiologic significance of variants of known melanoma susceptibility genes (MSGs) in families with multiple cases of melanoma.
  • Determine the proportion of multiple-case families that are explained by high-penetrance mutations in known MSGs.
  • Determine the proportion of multiple-case families that are explained by these mutations and whether it varies with latitude, as a surrogate for ultraviolet exposure, with number of affected relatives, with average age at onset of melanoma in relatives, with presence of multiple primary melanoma, or with other family-specific variables.
  • Determine the penetrance of MSG mutations in these families.
  • Determine if the penetrance varies with age, sex, or birth cohort.
  • Determine if the penetrance varies with the gene involved or nature of the mutation.
  • Assess the penetrance in mutations that also have a deleterious effect on the alternative splice product, p14ARF.
  • Determine whether carriers of MSGs have an increased susceptibility to other types of cancer.
  • Determine the risk of other types of cancers for mutation carriers.
  • Determine environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers.
  • Determine the cutaneous phenotypes that correlate with melanoma risk in these families.
  • Correlate cutaneous phenotypes with the presence of MSG variants.
  • Determine the effect of other covariates, such as sun exposure or the presence of alleles of putative modifying genes (e.g., MC1R or CDKN2A), on phenotype.
  • Determine if modifier genes, such as those controlling pigmentation of the skin, and therefore sun susceptibility, modify risk in MSG mutation carriers.
  • Identify any histopathological correlates of MSG status in primary tumors arising in melanoma-susceptible individuals in these families.
  • Identify any histopathological correlates of primary melanomas in carriers of MSG mutations with other covariates.

OUTLINE: This is a case-control, multicenter study.

Participants complete 2 questionnaires and assist in the creation and expansion of a family pedigree. Blood samples are examined for melanoma susceptibility gene mutations, including CDK4 and CDKN2A.

Participants are also examined for moles and photographed. Physical variables (e.g., skin, eye, and hair pigmentation) and sun damage (solar lentigines and freckling) are also noted.

If available, tissue samples are examined for Clark level, Breslow thickness, and frequency of mitoses. Peri-lesional skin from tumors is examined by p53 staining.

Participants are followed periodically to monitor cancer development.

Peer reviewed and funded or endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 5,000 participants will be accrued for this study.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Meets one of the following criteria:

    • Prior multiple primary melanomas

      • Histological samples available
    • Family history of melanoma, with melanoma in two first-degree relatives (e.g., cases of melanoma in both a mother and son or in two brothers but not in two cousins)
    • Family history of melanoma, where three or more individuals (of any relationship) have had melanoma


  • Not specified


  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00450593

United Kingdom
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Julia Newton Bishop, MD    44-113-206-4668      
Sponsors and Collaborators
Leeds Cancer Centre at St. James's University Hospital
Study Chair: Julia Newton Bishop, MD Leeds Cancer Centre at St. James's University Hospital
  More Information Identifier: NCT00450593     History of Changes
Other Study ID Numbers: CRUK-LCC-99/3/45
CDR0000532941 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: March 20, 2007
Last Updated: August 9, 2013

Keywords provided by National Cancer Institute (NCI):
hereditary multiple melanoma
recurrent melanoma
stage 0 melanoma
stage IV melanoma
stage IA melanoma
stage IB melanoma
stage IIA melanoma
stage IIB melanoma
stage IIC melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas processed this record on May 25, 2017