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Positional mapping for amplified DNA sequences on 1q21-q22 in hepatocellular carcinoma indicates candidate genes
Nathalie Wong1, Andrew Chan, Siu-Wah Lee
1Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., SAR Hong Kong, People's Republic of China. natwong@cuhk.edu.hk
Background/Aims:
Comparative genomic hybridization analysis on hepatocellular carcinoma (HCC) indicated frequent gains of 1q and an amplicon at 1q21-q22. Current cytogenetic evidences confer much importance on 1q21-q22, where a role in drug resistance, tumor metastasis and shorter patient survival had been implicated.
Methods:
Using positional mapping by interphase cytogenetics, we investigated the amplicon 1q21-q22 in five HCC cases. Three amplification maxima represented by yeast artificial chromosomes (YACs) 955E11, 876B11 and 945D5 that mapped to regions 1q21.1, 1q21.2 and 1q22, respectively, were indicated. We further investigated candidate genes expression in the mapped YACs by quantitative reverse-transcription-polymerase chain reaction. A panel of genes encoding protein transcripts involved in apoptosis, cell cycle progression, calcium binding and jumping translocation was studied.
Results:
Among ten HCC cases with the amplicon 1q21-q22 examined, we found a significant gene expression level of JTB, SHC1, CCT3 and COPA in the tumors than the paired adjacent non-malignant liver tissues (P< or =0.04).
Conclusions:
Our interphase findings on 1q21-q22 pinpointed three affected loci between D1S305 and D1S2369. Up-regulation of candidate genes identified within these over-represented regions may represent targets in the progression of HCC and may carry prognostic significance.