Document Detail


Molecular characterization of human cutaneous melanoma-derived cell lines.
MedLine Citation:
PMID:  22493355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Several studies have demonstrated that different genetic profiles contribute to melanoma development and progression.
MATERIALS AND METHODS: To evaluate the existence of different molecular aberration patterns in melanoma associated with v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or 9p21 locus alterations, eleven patient-derived melanoma cell lines were characterized. Multiplex ligation probe amplification (MLPA) was used to detect chromosomal alterations. Single- strand conformation analysis and sequencing were performed to study BRAF, neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (c-KIT), melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) (MC1R), cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4) genes.
RESULTS: BRAFV600E mutation was detected in 54% of cell lines. NRAS was mutated in one cell line also carrying multiple copies of NRAS. All cell lines with MC1R variants harboured BRAFV600E. Concurrent loss of MUTYH (1p33), gains of c-MYC (8q24) and of CDK6 (7q21) were found to be significantly associated in cell lines (45%) that harboured biallelic 9p21 deletions including CDKN2B-CDKN2A-MTAP.
CONCLUSION: These data suggest the existence of a specific pattern of somatic alterations in genes that are involved in DNA repair (MUTYH) and in cell cycle regulation (c-MYC, CDK6, CDKN2A and CDKN2B). Interestingly, all MC1R variants were associated with BRAFV600E and all cell lines from visceral metastases harboured BRAFV600E.
Authors:
Zighereda Ogbah; Joan Anton Puig-Butille; Federico Simonetta; Celia Badenas; Remedios Cervera; Jordi Milá; Daniel Benitez; Josep Malvehy; Ramon Vilella; Susana Puig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-05-24     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1245-51     Citation Subset:  IM    
Affiliation:
Melanoma Unit of the Department of Dermatology, Hospital Clínic of Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain. zigheog@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Line, Tumor
Cyclin-Dependent Kinase 4 / genetics
DNA Primers
Genes, ras
Humans
Melanoma / genetics*,  pathology
Mutation
Polymerase Chain Reaction
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins c-kit / genetics
Receptor, Melanocortin, Type 1 / genetics
Skin Neoplasms / genetics*,  pathology
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Receptor, Melanocortin, Type 1; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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