Integrated analysis of whole genome exon array and array-comparative genomic hybridization in gastric and colorectal cancer cells.

Abstract

Whole genome-scale integrated analyses of exon array and array-comparative genomic hybridization are expected to enable the identification of unknown genetic features of cancer cells. Here, we evaluated this approach in 22 gastric and colorectal cancer cell lines, focusing on protein kinase genes and genes belonging to the cadherin-catenin family. Regarding alternative splicing patterns, several cancer cell lines predominantly expressed isoform 1 of protein kinase A catalytic subunit beta (PRKACB). Paired gastric cancer specimens demonstrated that isoform 1 of PRKACB was a novel cancer-related variant transcript in gastric cancers. In addition, the exon array analysis clearly identified exon 3 or exon 3-4 skipping in catenin beta 1, a short intron insertion with exon 9 skipping in CDH1, and a deletional transcript of CDH13. These abnormal transcripts were shown to have arisen from small genomic deletions. Meanwhile, an integrated analysis of 11 gastric cancer cell lines revealed that four cell lines amplified fibroblast growth factor receptor 2, with truncated forms observed in two of the cell lines. Gene amplification, and not the truncated form, was found to determine the sensitivity to a fibroblast growth factor receptor inhibitor, indicating that our cell line panel might be useful for cell-based evaluations of specific inhibitors. Using an integrated analysis, we identified several abnormal transcripts and genomic alterations in gastric and colorectal cancer cells. Our approach might enable genetic changes to be identified more efficiently, and the present results warrant further investigation using clinical samples and integrated analyses.

• Authors: Kazuyuki Furuta, Tokuzo Arao, Kazuko Sakai, Hideharu Kimura, Tomoyuki Nagai, Daisuke Tamura, Keiichi Aomatsu, Kanae Kudo, Hiroyasu Kaneda, Yoshihiko Fujita, Kazuko Matsumoto, Yasuhide Yamada, Kazuyoshi Yanagihara, Masaru Sekijima, Kazuto Nishio
• Journal: Cancer science (Cancer Sci) Vol. 103 Issue 2 Pg. 221-7 (Feb 2012) ISSN: 1349-7006 [Electronic] England
• PMID: 22034905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• Cadherins
• Catenins
• Protein Isoforms
• Protein Kinases
• Receptor, Fibroblast Growth Factor, Type 2
• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
• PRKACB protein, human

Topics

• Alternative Splicing
• Base Sequence
• Cadherins (genetics)
• Catenins (genetics)
• Cell Line, Tumor
• Colorectal Neoplasms (genetics)
• Comparative Genomic Hybridization
• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits (genetics)
• Exons
• Gene Amplification
• Gene Dosage
• Genomics
• Humans
• Oligonucleotide Array Sequence Analysis (methods)
• Protein Isoforms (genetics)
• Protein Kinases (genetics)
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)
• Sequence Analysis, DNA
• Stomach Neoplasms (genetics)