title: Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis.
abstract: In this study, we used array-comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to examine genetic aberrations in melanoma cell lines and tissues. Array-comparative genomic hybridization revealed that the most frequent genetic changes found in melanoma cell lines were amplifications on chromosomes 7p and 20q, along with disruptions on Chr 9, 10, 11, 12, 22 and Y. Validation of the results using FISH on tissue microarrays (TMAs) identified TOP1 as being amplified in melanoma tissues. TOP1 amplification was detected in a high percentage (33%) of tumours and was associated with thicker, aggressive tumours. These results show that TOP1 amplification is associated with advanced tumours and poor prognosis in melanoma. These observations open the possibility that TOP1-targeted therapeutics may be of benefit in a particular subgroup of advanced stage melanoma patients.
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Denise
authors.initials: D
authors.lastname: Ryan
authors.forename: Mairin
authors.initials: M
authors.lastname: Rafferty
authors.forename: Shauna
authors.initials: S
authors.lastname: Hegarty
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Leary
authors.forename: William
authors.initials: W
authors.lastname: Faller
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gremel
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Margret
authors.initials: M
authors.lastname: Agnarsdottir
authors.forename: Sara
authors.initials: S
authors.lastname: Strömberg
authors.forename: Caroline
authors.initials: C
authors.lastname: Kampf
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Dervan
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
mesh_terms: D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis
chemical_list: D004264:DNA Topoisomerases, Type I