This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haluska, F. G. Articles by Goel, V. Search for Related Content PubMed PubMed Citation Articles by Haluska, F. G. Articles by Goel, V.

Genetic Alterations in Signaling Pathways in Melanoma

Authors' Affiliations:¹ Division of Hematology/Oncology and ² Department of Dermatology, Massashusetts General Hospital, Boston, Massachusetts and ³ University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Frank G. Haluska, New England Medical Center, 750 Washington St., Boston, MA 02111. Phone: 617-636-2626; Fax: 617-636-4367; E-mail: FHaluska{at}tufts-nemc.org.

Alterations in the RAS signaling cascade are almost uniformly present in melanoma. RAS itself is only infrequently mutated in melanoma although downstream of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the protein kinase B/Akt pathway. These genes are often altered in melanomas; indeed, the most frequent target of mutation in melanomas is BRAF, which is mutated in 60% to 70% of superficial spreading melanomas. These mutations occur in a background that is not normal, with the CDKN2A locus also typically being mutated. We review herein the data that suggest that the distribution of the signaling mutations is important. In general, melanomas carry a mutated NRAS, a mutated BRAF, or concurrent BRAF and PTEN mutations. These data support the hypothesis that the biochemical functions of RAS are portioned by mutations in the pathways lying downstream. Moreover, these mutations have no apparent relationship to the patterns of alteration of CDKN2A and its downstream effectors. Thus, the data also suggest that successful exploitation of mutations in melanoma will be dependent on understanding not only mutations and their frequency but their genetic context as well.

This article has been cited by other articles:

				C. Michailidou, M. Jones, P. Walker, J. Kamarashev, A. Kelly, and A. F. L. Hurlstone Dissecting the roles of Raf- and PI3K-signalling pathways in melanoma formation and progression in a zebrafish model Dis. Model. Mech., July 1, 2009; 2(7-8): 399 - 411. [Abstract] [Full Text] [PDF]

				C. Domenzain-Reyna, D. Hernandez, L. Miquel-Serra, M. J. Docampo, C. Badenas, A. Fabra, and A. Bassols Structure and Regulation of the Versican Promoter: THE VERSICAN PROMOTER IS REGULATED BY AP-1 AND TCF TRANSCRIPTION FACTORS IN INVASIVE HUMAN MELANOMA CELLS J. Biol. Chem., May 1, 2009; 284(18): 12306 - 12317. [Abstract] [Full Text] [PDF]

				S. Fedida-Metula, S. Elhyany, S. Tsory, S. Segal, M. Hershfinkel, I. Sekler, and D. Fishman Targeting lipid rafts inhibits protein kinase B by disrupting calcium homeostasis and attenuates malignant properties of melanoma cells Carcinogenesis, August 1, 2008; 29(8): 1546 - 1554. [Abstract] [Full Text] [PDF]