TY - JOUR
T1 - Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization
AU - Glatz-Krieger, Katharina
AU - Pache, Mona
AU - Tapia, Coya
AU - Fuchs, Alain
AU - Savic, Spasenija
AU - Glatz, Dieter
AU - Mihatsch, Michael
AU - Meyer, Peter
N1 - Funding Information:
Acknowledgements Katharina Glatz-Krieger and Coya Tapia had been supported by a grant from the “Schweizerische Nationalfonds” and the “SAKK”, respectively.
PY - 2006/9
Y1 - 2006/9
N2 - To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanomas.
AB - To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanomas.
KW - Amplification
KW - Fluorescence in situ hybridization
KW - Melanoma
KW - Tissue array
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U2 - 10.1007/s00428-006-0167-8
DO - 10.1007/s00428-006-0167-8
M3 - Article
C2 - 16523260
AN - SCOPUS:33748556546
SN - 0945-6317
VL - 449
SP - 328
EP - 333
JO - Virchows Archiv
JF - Virchows Archiv
IS - 3
ER -