Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis

Denise Ryan; Mairin Rafferty; Shauna Hegarty; Patrick O'Leary; William Faller; Gabriela Gremel; Michael Bergqvist; Margret Agnarsdottir; Sara Strömberg; Caroline Kampf; Fredrik Pontén; Robert C Millikan; Peter A Dervan; William M Gallagher

doi:10.1111/j.1755-148X.2010.00720.x

Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis

Denise Ryan, Mairin Rafferty, Shauna Hegarty, Patrick O'Leary, William Faller, Gabriela Gremel, Michael Bergqvist, Margret Agnarsdottir, Sara Strömberg, Caroline Kampf, Fredrik Pontén, Robert C Millikan, Peter A Dervan, William M Gallagher

School of Biochemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	542-53
Number of pages	12
Journal	Pigment Cell & Melanoma Research
Volume	23
Issue number	4
DOIs	https://doi.org/10.1111/j.1755-148X.2010.00720.x
Publication status	Published - Aug 2010

Keywords

Cell Line, Tumor
Comparative Genomic Hybridization
DNA Topoisomerases, Type I/genetics
Gene Amplification
Humans
In Situ Hybridization, Fluorescence
Male
Melanoma/diagnosis
Prognosis

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Ryan, D., Rafferty, M., Hegarty, S., O'Leary, P., Faller, W., Gremel, G., Bergqvist, M., Agnarsdottir, M., Strömberg, S., Kampf, C., Pontén, F., Millikan, R. C., Dervan, P. A., & Gallagher, W. M. (2010). Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis. Pigment Cell & Melanoma Research, 23(4), 542-53. https://doi.org/10.1111/j.1755-148X.2010.00720.x

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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.",

keywords = "Cell Line, Tumor, Comparative Genomic Hybridization, DNA Topoisomerases, Type I/genetics, Gene Amplification, Humans, In Situ Hybridization, Fluorescence, Male, Melanoma/diagnosis, Prognosis",

author = "Denise Ryan and Mairin Rafferty and Shauna Hegarty and Patrick O'Leary and William Faller and Gabriela Gremel and Michael Bergqvist and Margret Agnarsdottir and Sara Str{\"o}mberg and Caroline Kampf and Fredrik Pont{\'e}n and Millikan, \{Robert C\} and Dervan, \{Peter A\} and Gallagher, \{William M\}",

year = "2010",

month = aug,

doi = "10.1111/j.1755-148X.2010.00720.x",

language = "English",

volume = "23",

pages = "542--53",

journal = "Pigment Cell \& Melanoma Research",

issn = "1755-148X",

publisher = "Wiley",

number = "4",

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Ryan, D, Rafferty, M, Hegarty, S, O'Leary, P, Faller, W, Gremel, G, Bergqvist, M, Agnarsdottir, M, Strömberg, S, Kampf, C, Pontén, F, Millikan, RC, Dervan, PA & Gallagher, WM 2010, 'Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis', Pigment Cell & Melanoma Research, vol. 23, no. 4, pp. 542-53. https://doi.org/10.1111/j.1755-148X.2010.00720.x

TY - JOUR

T1 - Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis

AU - Ryan, Denise

AU - Rafferty, Mairin

AU - Hegarty, Shauna

AU - O'Leary, Patrick

AU - Faller, William

AU - Gremel, Gabriela

AU - Bergqvist, Michael

AU - Agnarsdottir, Margret

AU - Strömberg, Sara

AU - Kampf, Caroline

AU - Pontén, Fredrik

AU - Millikan, Robert C

AU - Dervan, Peter A

AU - Gallagher, William M

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Comparative Genomic Hybridization

KW - DNA Topoisomerases, Type I/genetics

KW - Gene Amplification

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Male

KW - Melanoma/diagnosis

KW - Prognosis

U2 - 10.1111/j.1755-148X.2010.00720.x

DO - 10.1111/j.1755-148X.2010.00720.x

M3 - Article (Academic Journal)

C2 - 20465595

SN - 1755-148X

VL - 23

SP - 542

EP - 553

JO - Pigment Cell & Melanoma Research

JF - Pigment Cell & Melanoma Research

IS - 4

ER -

Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis

Abstract

Keywords

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