Journal Article

Resequencing and copy number analysis of the human tyrosine kinase gene family in poorly differentiated gastric cancer

Takashi Kubo, Yukie Kuroda, Hiroko Shimizu, Akiko Kokubu, Naoko Okada, Fumie Hosoda, Yasuhito Arai, Yu Nakamura, Hirokazu Taniguchi, Kazuyoshi Yanagihara, Issei Imoto, Johji Inazawa, Setsuo Hirohashi and Tatsuhiro Shibata

in Carcinogenesis

Volume 30, issue 11, pages 1857-1864
Published in print November 2009 | ISSN: 0143-3334
Published online September 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp206
Resequencing and copy number analysis of the human tyrosine kinase gene family in poorly differentiated gastric cancer

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The tyrosine kinase (TK) family is an important regulator of signaling pathways that control a variety of physiological and pathological conditions, and a substantial proportion of TK genes are genetically altered in cancer. To clarify the somatic mutation profile of TK genes and discover potential targets for gastric cancer (GC) therapy, we undertook a systematic screening of mutations in the kinase domains of all human TK genes (636 exons of 90 genes) in 17 GC cell lines and 52 microdissected primary GCs with poorly differentiated histology. We identified 26 non-synonymous alterations (22 genes in total) that included 11 sequence alterations in cell lines and 15 somatic mutations in primary tumors. Recurrent mutations were found in four genes including a known oncogene (NTRK3), the Src kinase family (LTK and CSK) and a potential Wnt signal activator (ROR2). In addition, we analyzed copy number alterations of all the TK gene loci in the same cohort samples by array-based comparative genomic hybridization analysis and identified 24 high-level amplifications and two homozygous deletions. Both sequence alteration and frequent copy number aberration were detected in two TK genes (HCK and ERBB2), strongly suggesting that they encode potential oncogenes in GC. Our focused and integrated analyses of systemic resequencing and gene copy number have revealed the novel onco-kinome profile of GC and pave the way to a comprehensive understanding of the GC genome.

Journal Article.  4840 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.