Overexpression of genes on 16q associated with cisplatin resistance of testicular germ cell tumor cell lines.
Testicular germ-cell tumors (TGCTs) show exquisite sensitivity to cisplatin-based chemotherapy, and therefore this is considered a good model system for studying the mechanism of chemotherapy resistance. Although the genetic alterations related to TGCT have been well studied, little is known about the genetic basis of chemotherapy resistance, which occurs in a small proportion of TGCTs. In this study, we investigated genomic and expression differences between three cisplatin-sensitive and their paired cisplatin-resistant lines using combined whole-genome screen approaches. Comparative genomic hybridization (CGH) analysis on chromosomes revealed genetic differences between the resistant and parent cell lines in each pair, but did not show any consistent chromosome changes in all three lines. Microarray CGH analysis generated some additional information of DNA copy number gains and losses including some important oncogenes, tumor-suppressor genes, and drug-resistance-related genes. However, no consistent genomic region changes were found in the three cell lines. Interestingly, when comparative expressed sequence hybridization, a technique for gene expression profiling along chromosomes, was applied, we discovered a consistently overexpressed chromosomal region in all three resistant lines compared with their parent lines. The minimum overlapping chromosomal region is at 16q22-23. Further definition of genes in this chromosomal region will aid our understanding of the mechanism of cisplatin resistance and may offer novel therapeutic targets.
Wilson
Charlotte
C
Department of Medical Oncology, Barts and London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, United Kingdom.
Yang
Jinshu
J
Strefford
Jon C
JC
Summersgill
Brenda
B
Young
Bryan D
BD
Shipley
Janet
J
Oliver
Tim
T
Lu
Yong-Jie
YJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002885:Chromosomes, Human, Pair 16; D002945:Cisplatin / Q000494:pharmacology*; D018237:Germinoma / Q000235:genetics*; D006801:Humans; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics*
D000970:Antineoplastic Agents; D002945:Cisplatin