title: Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene.
abstract: 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.
authors.affiliation: Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia. Ken.Dutton-Regester@qimr.edu.au
authors.forename: Ken
authors.initials: K
authors.lastname: Dutton-Regester
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Aoude
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Nancarrow
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Stark
authors.forename: Linda
authors.initials: L
authors.lastname: O'Connor
authors.forename: Cathy
authors.initials: C
authors.lastname: Lanagan
authors.forename: Gulietta M
authors.initials: GM
authors.lastname: Pupo
authors.forename: Varsha
authors.initials: V
authors.lastname: Tembe
authors.forename: Candace D
authors.initials: CD
authors.lastname: Carter
authors.forename: Michael
authors.initials: M
authors.lastname: O'Rourke
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Schmidt
authors.forename: Adrian
authors.initials: A
authors.lastname: Herington
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
mesh_terms: D045744:Cell Line, Tumor; D005784:Gene Amplification; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011506:Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins
chemical_list: D011506:Proteins; C096163:TFG protein, human; D033921:Vesicular Transport Proteins