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Identification of TFG (TRK‐fused gene) as a putative metastatic melanoma tumor suppressor gene
Author(s) -
DuttonRegester Ken,
Aoude Lauren G.,
Nancarrow Derek J.,
Stark Mitchell S.,
O'Connor Linda,
Lanagan Cathy,
Pupo Gulietta M.,
Tembe Varsha,
Carter Candace D.,
O'Rourke Michael,
Scolyer Richard A.,
Mann Graham J.,
Schmidt Christopher W.,
Herington Adrian,
Hayward Nicholas K.
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21932
Subject(s) - neuroblastoma ras viral oncogene homolog , cdkn2a , melanoma , microphthalmia associated transcription factor , biology , cancer research , cdkn2b , gene , bap1 , copy number variation , genetics , copy number analysis , pten , mutation , genome , pi3k/akt/mtor pathway , signal transduction , transcription factor , kras
High density SNP arrays can be used to identify DNA copy number changes in tumors such as homozygous deletions of tumor suppressor genes and focal amplifications of oncogenes. Illumina Human CNV370 Bead chip arrays were used to assess the genome for unbalanced chromosomal events occurring in 39 cell lines derived from stage III metastatic melanomas. A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39). In addition, a number of focal homozygous deletions potentially targeting novel melanoma tumor suppressor genes were identified. Because of their likely functional significance for melanoma progression, FAS , CH25H , BMPR1A , ACTA2 , and TFG were investigated in a larger cohort of melanomas through sequencing. Nonsynonymous mutations were identified in BMPR1A (1 of 43), ACTA2 (3 of 43), and TFG (5 of 103). A number of potentially important mutation events occurred in TFG including the identification of a mini mutation “hotspot” at amino acid residue 380 (P380S and P380L) and the presence of multiple mutations in two melanomas. Mutations in TFG may have important clinical relevance for current therapeutic strategies to treat metastatic melanoma. © 2012 Wiley Periodicals, Inc.