title: Copy number gains in 11q13 and 8q24 [corrected] are highly linked to prognosis in cutaneous malignant melanoma.
abstract: Relating specific genetic alterations to prognosis may help improve prognostication in melanoma, may identify key oncogenic drivers in cancer, and may assist in developing targeted therapies. Characteristic genetic alterations in melanoma include chromosomal copy number aberrations. We evaluated 97 melanomas (55 metastasizing and 42 nonmetastasizing) after a minimum 5-year follow-up in a case-control study using fluorescence in situ hybridization, targeting commonly altered chromosomal loci in melanoma. Eight probes arranged in two panels were used, and 11 parameters were evaluated. Parameters showing a statistically significant difference between the metastasizing and nonmetastasizing groups were evaluated with multivariate logistic regression analysis to compare their prognostic potential with other traditional prognostic markers used by the American Joint Committee on Cancer. Four of 11 parameters evaluated, including CCND1 (alias Bcl-1) gain, CCND1 r-gain, MYC (alias c-myc) gain, and MYC r-gain, had a statistically significant difference in the metastasizing versus nonmetastasizing group. All four parameters maintained statistical significance when evaluated in separate multivariate logistic regression analyses that included the seven currently used American Joint Commission on Cancer prognosticators in melanoma. In multivariate analyses, these four parameters were second only to ulceration in their prognostic potential. Copy number changes at 11q13 and 8q24 [corrected] harboring CCND1 and MYC, respectively, are highly associated with prognosis. Fluorescence in situ hybridization targeting these loci may be a useful standardized prognostic marker in melanoma skin cancer.
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N. St Clair Street, Chicago, IL 60611, USA. pedram.gerami@nmff.org
authors.forename: Pedram
authors.initials: P
authors.lastname: Gerami
authors.forename: Susan S
authors.initials: SS
authors.lastname: Jewell
authors.forename: Pedram
authors.initials: P
authors.lastname: Pouryazdanparast
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Wayne
authors.forename: Zahra
authors.initials: Z
authors.lastname: Haghighat
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Larry
authors.initials: L
authors.lastname: Morrison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11; D002898:Chromosomes, Human, Pair 8; D019938:Cyclin D1 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1