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Frequent gene copy number changes and BRAF V600E gene mutation in conjunctival melanoma
Author(s) -
JMOR F,
LAKE SL,
TAKTAK AFG,
DAMATO BE,
COUPLAND SE
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.476.x
Subject(s) - gene , mutation , melanoma , v600e , genetics , cancer research , medicine , biology
Purpose The molecular aetiology of conjunctival melanoma (CM) is poorly understood as few studies have investigated the genetic changes in this tumour. This study investigated the copy number of all autosome arms, genes known to be frequently altered in tumourigenesis, and BRAF V600E mutation, in CMs using multiplex ligation‐dependent probe amplification (MLPA). Methods Three MLPA assays were performed (P027, P036, P206) using DNA extracted from 32 primary and metastatic, formalin‐fixed, paraffin‐embedded CM samples. Results CDKN1A and RUNX2 were amplified in over 60% and 75% of primary CM, respectively. MLH1 and TIMP2 were frequently amplified, and MGMT and ECHS1 were frequently deleted, in metastatic CMs. BRAF V600E mutations were identified in 6/12 primary CMs and 4/6 metastatic CMs. The P036 assay detects copy number of genes, not known to be involved in tumourigenesis, in the subtelomeric regions of all autosomes. Genes found by this assay to be frequently deleted in metastatic CM were BDH, FLJ20265, PAO and OPRL1. No statistically significant association with BRAF mutation, or changes in copy number, and gender, age, histological cell type or survival time, were identified. Conclusion Despite no copy number changes occurring exclusively in metastatic CM changes in the MLH1, TIMP2, MGMT and ECHS1 were observed more frequently. Amplification of subtelomeric genes BDH (3q), FLJ20265 (4p), PAO (10q) and OPRL1 (20q) may indicate common gain of the respective chromosome arms in metastatic CM. Further investigation of these loci in a larger cohort of tumours may identify those CM more likely to metastasize and elucidate the cell signalling pathways that are deregulated in CM, thereby facilitating future treatment of patients.