Molecular genetics of familial cutaneous melanoma.
FG Haluska, FS Hodi - Journal of clinical oncology, 1998 - ascopubs.org
FG Haluska, FS Hodi
Journal of clinical oncology, 1998•ascopubs.orgPURPOSE A family history of melanoma is a significant risk factor for the disease, and
recently several loci that determine susceptibility to the development of melanoma have
been identified. The most important of these is p16/CDKN2A. We attempted to determine the
degree to which the p16/CDKN2A gene has been implicated in the development of
melanoma, and to identify other genetic factors that play a role as well. METHODS We
reviewed the literature published since the isolation of p16/CDKN2A and identified 13 …
recently several loci that determine susceptibility to the development of melanoma have
been identified. The most important of these is p16/CDKN2A. We attempted to determine the
degree to which the p16/CDKN2A gene has been implicated in the development of
melanoma, and to identify other genetic factors that play a role as well. METHODS We
reviewed the literature published since the isolation of p16/CDKN2A and identified 13 …
PURPOSE
A family history of melanoma is a significant risk factor for the disease, and recently several loci that determine susceptibility to the development of melanoma have been identified. The most important of these is p16/CDKN2A. We attempted to determine the degree to which the p16/CDKN2A gene has been implicated in the development of melanoma, and to identify other genetic factors that play a role as well.
METHODS
We reviewed the literature published since the isolation of p16/CDKN2A and identified 13 studies that report the status of the gene in melanoma samples and 12 reports that examine p16/CDKN2A in melanoma kindreds. We also reviewed associated studies on CDK4 and RB1 involvement in melanoma, and examined the role of p16/CDKN2A in other inherited cancers.
RESULTS
The evidence strongly implicates p16/CDKN2A in determining predisposition to malignant melanoma. Overall, approximately 20% of families that have been studied show mutations in the gene. However, because of clustering of sporadic cases in families, and potentially because of technical factors, this is likely an underestimate of the proportion of the genetic predisposition for melanoma that is due to p16/CDKN2A mutation. Rare families carry a mutated CDK4 gene that is also responsible for inherited melanoma.
CONCLUSION
The gene p16/CDKN2A is an important determinant of melanoma risk. A commercial test is presently available to assess the status of this locus. However, because of uncertainties regarding the interpretation of the results of p16/CDKN2A genetic testing, we do not recommend routine clinical use of this test at this time.
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