Gene-specific fluorescence in-situ hybridization analysis... : Melanoma Research (original) (raw)

ORIGINAL ARTICLES

Gene-specific fluorescence in-situ hybridization analysis on tissue microarray to refine the region of chromosome 20q amplification in melanoma

Koynova, Denitsa K.a; Jordanova, Ekaterina S.d; Milev, Angel D.b; Dijkman, Remcoe; Kirov, Krassimir S.c; Toncheva, Draga I.a; Gruis, Nelleke A.e

aDepartment of Medical Genetics, Medical University

Departments of bPathology

cDermatology, National Center of Oncology, Sofia, Bulgaria

dDepartments of Pathology

eDermatology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence and requests for reprints to Dr Nelleke A. Gruis, PhD, LUMC Skin Research Lab, Room T-02-034, S2-P, PO Box 9600, 2300 RC Leiden, The Netherlands

Tel: +31-71-5269366; e-mail: [email protected]

Received 15 June 2006 Accepted 8 November 2006

Abstract

Several comparative genomic hybridization studies provide evidence for overrepresentation of the long arm of chromosome 20 in malignant melanoma. These studies also suggest that chromosome 20q contains genes that may contribute to melanoma pathogenesis. To refine the region of 20q amplification and to identify potential candidate genes involved in melanoma or even in melanoma progression from these regions, we combined fluorescence in-situ hybridization with MYBL2, ZNF217, CYP24 and STK6 specific probes (chromosomal region 20q13.1–q13.2) with high-throughput tissue microarray consisting of 280 primary melanomas and melanoma metastases. Low-level amplification ranging from 0.5 to 2.0% was detected for the tumor-related genes of interest. Higher frequencies of gain when compared with amplification were detected for MYBL2, ZNF217, CYP24 and STK6. Aneusomy of centromere 20 was observed in 29.9% of the analyzed tumors. A significantly higher frequency of ZNF217, CYP24 and STK6 total copy-number increase, as well as aneusomy of centromere 20, was found in the group of metastases when compared with the group of primary melanomas. Despite the technological advantage of fluorescence in-situ hybridization on tissue microarray, which allows refining regions of amplification, we were not able to recognize any of the MYBL2, ZNF217, CYP24 and STK6 genes as a particular relevant gene for melanoma tumorigenesis.