Genetic alterations in RAS-regulated pathway in acral lentiginous melanoma.
Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS-related pathways are present in 87.5% of acral lentiginous melanomas.
Centro Investigación Biomédica en Enfermedades Raras, ISCIII, Barcelona, Spain.
Joan A
JA
Puig-Butillé
Celia
C
Badenas
Zighereda
Z
Ogbah
Cristina
C
Carrera
Paula
P
Aguilera
Josep
J
Malvehy
Susana
S
Puig
D017209:Apoptosis; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002453:Cell Cycle; D002872:Chromosome Deletion; D016000:Cluster Analysis; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D014644:Genetic Variation; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020125:Mutation, Missense; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
C530104:CCND1 protein, human; D008565:Membrane Proteins; D019938:Cyclin D1; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; C482119:BRAF protein, human; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human