Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis.
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.
Ryan
Denise
D
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Rafferty
Mairin
M
Hegarty
Shauna
S
O'Leary
Patrick
P
Faller
William
W
Gremel
Gabriela
G
Bergqvist
Michael
M
Agnarsdottir
Margret
M
Strömberg
Sara
S
Kampf
Caroline
C
Pontén
Fredrik
F
Millikan
Robert C
RC
Dervan
Peter A
PA
Gallagher
William M
WM
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
D004264:DNA Topoisomerases, Type I