title: Mutation stability in primary and metastatic melanoma: what we know and what we don't.
abstract: Despite the efficacy and success of targeted therapies, a significant number of patients with melanoma exhibit either intrinsic or acquired resistance to these drugs. Numerous mechanisms for the development of resistance have been postulated, but the precise reason for this is not known. In this review, we examine the incidence of mutations in select genes (BRAF, NRAS, C-KIT, and GNAQ) known to occur in melanoma, specifically in primary tumors and their paired metastases, to understand the significance of intratumoral heterogeneity by assessing how changes in mutation status alters the process of metastatic spread. Our data revealed a small yet consistent degree of discordance of mutations in the MAPK pathway commonly occurring in melanoma indicating that failed targeted therapy may be a consequence of this.
authors.affiliation: Jefferson Medical College, Philadelphia, PA, USA.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Varada
authors.affiliation: VA Boston Healthcare System, New England Department of Pathology and Laboratory Medcine (113), West Roxbury, MA, USA. me@meeramahalingam.com.
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
mesh_terms: D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D008565:Membrane Proteins / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017211:Treatment Failure
chemical_list: C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11