Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene
Corresponding Author
Ken Dutton-Regester
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Faculty of Science and Technology, Queensland University of Technology, Brisbane QLD 4000, Australia
300 Herston Rd, Herston 4029 QLD, AustraliaSearch for more papers by this authorLauren G. Aoude
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorDerek J. Nancarrow
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorMitchell S. Stark
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorLinda O'Connor
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorCathy Lanagan
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorGulietta M. Pupo
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorVarsha Tembe
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorCandace D. Carter
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorMichael O'Rourke
Morris Tower, 149 Wickham Tce Brisbane 4000 QLD, Australia
Search for more papers by this authorRichard A. Scolyer
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Department Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050 Australia
Discipline of Pathology, Sydney Medical School, the University of Sydney, NSW, 2006 Australia
Search for more papers by this authorGraham J. Mann
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorChristopher W. Schmidt
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorAdrian Herington
Faculty of Science and Technology, Queensland University of Technology, Brisbane QLD 4000, Australia
Search for more papers by this authorNicholas K. Hayward
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorCorresponding Author
Ken Dutton-Regester
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Faculty of Science and Technology, Queensland University of Technology, Brisbane QLD 4000, Australia
300 Herston Rd, Herston 4029 QLD, AustraliaSearch for more papers by this authorLauren G. Aoude
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorDerek J. Nancarrow
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorMitchell S. Stark
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorLinda O'Connor
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorCathy Lanagan
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorGulietta M. Pupo
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorVarsha Tembe
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorCandace D. Carter
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorMichael O'Rourke
Morris Tower, 149 Wickham Tce Brisbane 4000 QLD, Australia
Search for more papers by this authorRichard A. Scolyer
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Department Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050 Australia
Discipline of Pathology, Sydney Medical School, the University of Sydney, NSW, 2006 Australia
Search for more papers by this authorGraham J. Mann
University of Sydney at Westmead Millennium Institute, Westmead NSW 2145, Australia
Melanoma Institute of Australia (Formerly the Sydney Melanoma Unit), North Sydney, NSW 2060, Australia
Search for more papers by this authorChristopher W. Schmidt
Queensland Institute of Medical Research, Cancer Immunotherapy Laboratory, Brisbane QLD, 4006 Australia
Search for more papers by this authorAdrian Herington
Faculty of Science and Technology, Queensland University of Technology, Brisbane QLD 4000, Australia
Search for more papers by this authorNicholas K. Hayward
Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane QLD 4006, Australia
Search for more papers by this authorAbstract
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.
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