Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas

Hye Eun Kim, Dae Ghon Kim, Kyung Jin Lee, Jang Geun Son, Min Young Song, Young Mi Park, Jae Jung Kim, Sung Won Cho, Sung Gil Chi, Hyun Sub Cheong, Hyoung Doo Shin, Sang Wook Lee, Jong Keuk Lee

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Genomic changes frequently occur in cancer cells during tumorigenesis from normal cells. Using the Illumina Human NS-12 single-nucleotide polymorphism (SNP) chip to screen for gene copy number changes in primary hepatocellular carcinomas (HCCs), we initially detected amplification of 35 genes from four genomic regions (1q21-41, 6p21.2-24.1, 7p13 and 8q13-23). By integrated screening of these genes for both DNA copy number and gene expression in HCC and colorectal cancer, we selected CENPF (centromere protein F/mitosin), GMNN (geminin, DNA replication inhibitor), CDK13 (cyclin-dependent kinase 13), and FAM82B (family with sequence similarity 82, member B) as common cancer genes. Each gene exhibited an amplification frequency of ~30% (range, 20-50%) in primary HCC (n = 57) and colorectal cancer (n = 12), as well as in a panel of human cancer cell lines (n = 70). Clonogenic and invasion assays of NIH3T3 cells transfected with each of the four amplified genes showed that CENPF, GMNN, and CDK13 were highly oncogenic whereas FAM82B was not. Interestingly, the oncogenic activity of these genes (excluding FAM82B) was highly correlated with gene-copy numbers in tumor samples (correlation coefficient, r>0.423), indicating that amplifications of CENPF, GMNN, and CDK13 genes are tightly linked and coincident in tumors. Furthermore, we confirmed that CDK13 gene copy number was significantly associated with clinical onset age in patients with HCC (P = 0.0037). Taken together, our results suggest that coincidently amplified CDK13, GMNN, and CENPF genes can play a role as common cancer-driver genes in human cancers.

Original languageEnglish
Article numbere43223
JournalPloS one
Volume7
Issue number8
DOIs
Publication statusPublished - 2012 Aug 13

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas'. Together they form a unique fingerprint.

  • Cite this

    Kim, H. E., Kim, D. G., Lee, K. J., Son, J. G., Song, M. Y., Park, Y. M., Kim, J. J., Cho, S. W., Chi, S. G., Cheong, H. S., Shin, H. D., Lee, S. W., & Lee, J. K. (2012). Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PloS one, 7(8), [e43223]. https://doi.org/10.1371/journal.pone.0043223