PURPOSE: Gene copy number alteration (CNA) is common in malignant melanoma and is associated with tumor development and progression. The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma. EXPERIMENTAL DESIGN: A panel of 16 locus-specific fluorescence in situ hybridization (FISH) probes located on eight chromosomes was used to identify CNA in touch preparations of frozen tissue samples from 19 patients with metastatic melanoma (SWOG-9431). A subset (n = 11) was analyzed using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) of DNA isolated directly from touch-preparation slides. RESULTS: By FISH, most samples showed loss near or at WISP3/6p21, CCND3/6q22, and CDKN2A/9p21 (>75% of samples tested). More than one third of CDKN2A/9p21 losses were biallelic. Gains of NEDD9/6p24, MET/7q31, and MYC/8q24 were common (57%, 47%, and 41%, respectively) and CNA events involving 9p21/7p12.3 and MET were frequently coincident, suggesting gain of the whole chromosome 7. Changes were confirmed by aCGH, which also uncovered many discreet regions of change, larger than a single BAC. Overlapping segments observed in >45% of samples included many of the loci analyzed in the FISH study, in addition to other WNT pathway members, and genes associated with TP53 pathways and DNA damage response, repair, and stability. CONCLUSIONS: This study outlines a set of CNAs at the gene and regional level, using FISH and aCGH, which may provide a benchmark for future studies and may be important in selection of individual therapy for patients with metastatic malignant melanoma.
PURPOSE: Gene copy number alteration (CNA) is common in malignant melanoma and is associated with tumor development and progression. The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma. EXPERIMENTAL DESIGN: A panel of 16 locus-specific fluorescence in situ hybridization (FISH) probes located on eight chromosomes was used to identify CNA in touch preparations of frozen tissue samples from 19 patients with metastatic melanoma (SWOG-9431). A subset (n = 11) was analyzed using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) of DNA isolated directly from touch-preparation slides. RESULTS: By FISH, most samples showed loss near or at WISP3/6p21, CCND3/6q22, and CDKN2A/9p21 (>75% of samples tested). More than one third of CDKN2A/9p21 losses were biallelic. Gains of NEDD9/6p24, MET/7q31, and MYC/8q24 were common (57%, 47%, and 41%, respectively) and CNA events involving 9p21/7p12.3 and MET were frequently coincident, suggesting gain of the whole chromosome 7. Changes were confirmed by aCGH, which also uncovered many discreet regions of change, larger than a single BAC. Overlapping segments observed in >45% of samples included many of the loci analyzed in the FISH study, in addition to other WNT pathway members, and genes associated with TP53 pathways and DNA damage response, repair, and stability. CONCLUSIONS: This study outlines a set of CNAs at the gene and regional level, using FISH and aCGH, which may provide a benchmark for future studies and may be important in selection of individual therapy for patients with metastatic malignant melanoma.
Authors: Matthew W Vanbrocklin; James P Robinson; Todd Whitwam; Adam R Guilbeault; Julie Koeman; Pamela J Swiatek; George F Vande Woude; Joseph D Khoury; Sheri L Holmen Journal: Pigment Cell Melanoma Res Date: 2009-04-29 Impact factor: 4.693
Authors: Anjali S Advani; Holly M Gundacker; Olga Sala-Torra; Jerald P Radich; Raymond Lai; Marilyn L Slovak; Jeffrey E Lancet; Steve E Coutre; Robert K Stuart; Martha P Mims; Patrick J Stiff; Frederick R Appelbaum Journal: Br J Haematol Date: 2010-12 Impact factor: 6.998
Authors: Marilyn L Slovak; Victoria Bedell; Ya-Hsuan Hsu; Dolores B Estrine; Norma J Nowak; Maria L Delioukina; Lawrence M Weiss; David D Smith; Stephen J Forman Journal: Clin Cancer Res Date: 2011-03-08 Impact factor: 12.531
Authors: Emma Shtivelman; Michael Q A Davies; Patrick Hwu; James Yang; Michal Lotem; Moshe Oren; Keith T Flaherty; David E Fisher Journal: Oncotarget Date: 2014-04-15
Authors: Frances P Noonan; M Raza Zaidi; Agnieszka Wolnicka-Glubisz; Miriam R Anver; Jesse Bahn; Albert Wielgus; Jean Cadet; Thierry Douki; Stephane Mouret; Margaret A Tucker; Anastas Popratiloff; Glenn Merlino; Edward C De Fabo Journal: Nat Commun Date: 2012-06-06 Impact factor: 14.919