Document Detail

Tandem BRAF mutations in primary invasive melanomas.
MedLine Citation:
PMID:  15140228     Owner:  NLM     Status:  MEDLINE    
The RAS/RAF/MAPK pathway likely mediates critical cell proliferation and survival signals in melanoma. BRAF mutations have been found in a high percentage of melanoma cell lines and metastases; however, only a few studies with a limited number of specimens have focused on primary melanomas. We examined BRAF exon 15 mutational status in 37 primary invasive melanomas of varying thicknesses, which had undergone a standardized pathology review. BRAF mutational status was determined using direct manual sequencing of PCR products, followed by resequencing separately amplified DNA aliquots to confirm each mutation. BRAF exon 15 mutations were found in 17 of 37 (46%) primary melanomas. Tumor-specific tandem mutations, encoding either V599K, V599R, or V599E, were found in 5 of 17 (29%) melanomas with BRAF exon 15 mutations. Cloning of BRAF double base-pair substitutions confirmed that both base changes were on the same allele and can result in a positive charge at codon 599. BRAF mutations, including tandem mutations, were frequently found in both thin and thick primary melanomas, implying that these mutations can occur early in the progression of melanoma. The finding of tandem mutations in thin melanomas makes it more likely that they arise as a simultaneous rather than sequential event.
Nancy E Thomas; Audrey Alexander; Sharon N Edmiston; Eloise Parrish; Robert C Millikan; Marianne Berwick; Pamela Groben; David W Ollila; Dianne Mattingly; Kathleen Conway
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  122     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-13     Completed Date:  2004-06-25     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1245-50     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Base Sequence
DNA Mutational Analysis
Melanoma / genetics*,  pathology
Middle Aged
Molecular Sequence Data
Point Mutation*
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf / genetics*
Skin Neoplasms / genetics*,  pathology
Grant Support
P30 CA118100/CA/NCI NIH HHS; R01 CA112243/CA/NCI NIH HHS; R01 CA112243-03/CA/NCI NIH HHS; R01 CA112524/CA/NCI NIH HHS; R03 CA103089/CA/NCI NIH HHS; R03 CA103089/CA/NCI NIH HHS; R03 CA103089-01/CA/NCI NIH HHS; U01 CA083180/CA/NCI NIH HHS; U01-CA83180/CA/NCI NIH HHS
Reg. No./Substance:
EC protein, human; EC Proteins B-raf; EC Proteins c-raf
Comment In:
J Invest Dermatol. 2004 May;122(5):VII-VIII   [PMID:  15140248 ]

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