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Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer.

Publication ,  Journal Article
Hou, Q; Wu, YH; Grabsch, H; Zhu, Y; Leong, SH; Ganesan, K; Cross, D; Tan, LK; Tao, J; Gopalakrishnan, V; Tang, BL; Kon, OL; Tan, P
Published in: Cancer Res
June 15, 2008

Recurrent genomic amplifications and deletions are frequently observed in primary gastric cancers (GC). However, identifying specific oncogenes and tumor suppressor genes within these regions can be challenging, as they often cover tens to hundreds of genes. Here, we combined high-resolution array-based comparative genomic hybridization (aCGH) with gene expression profiling to target genes within focal high-level amplifications in GC cell lines, and identified RAB23 as an amplified and overexpressed Chr 6p11p12 gene in Hs746T cells. High RAB23 protein expression was also observed in some lines lacking RAB23 amplification, suggesting additional mechanisms for up-regulating RAB23 besides gene amplification. siRNA silencing of RAB23 significantly reduced cellular invasion and migration in Hs746T cells, whereas overexpression of RAB23 enhanced cellular invasion in AGS cells. RAB23 amplifications in primary gastric tumors were confirmed by both fluorescence in situ hybridization and genomic qPCR, and in two independent patient cohorts from Hong Kong and the United Kingdom RAB23 expression was significantly associated with diffuse-type GC (dGC) compared with intestinal-type GC (iGC). These results provide further evidence that dGC and iGC likely represent two molecularly distinct tumor types, and show that investigating focal chromosomal amplifications by combining high-resolution aCGH with expression profiling is a powerful strategy for identifying novel cancer genes in regions of recurrent chromosomal aberration.

Duke Scholars

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2008

Volume

68

Issue

12

Start / End Page

4623 / 4630

Location

United States

Related Subject Headings

  • rab GTP-Binding Proteins
  • Tumor Cells, Cultured
  • Tissue Array Analysis
  • Stomach Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
 

Citation

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Hou, Q., Wu, Y. H., Grabsch, H., Zhu, Y., Leong, S. H., Ganesan, K., … Tan, P. (2008). Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res, 68(12), 4623–4630. https://doi.org/10.1158/0008-5472.CAN-07-5870
Hou, Qingsong, Yong Hui Wu, Heike Grabsch, Yansong Zhu, Siew Hong Leong, Kumaresan Ganesan, Debra Cross, et al. “Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer.Cancer Res 68, no. 12 (June 15, 2008): 4623–30. https://doi.org/10.1158/0008-5472.CAN-07-5870.
Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K, et al. Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res. 2008 Jun 15;68(12):4623–30.
Hou, Qingsong, et al. “Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer.Cancer Res, vol. 68, no. 12, June 2008, pp. 4623–30. Pubmed, doi:10.1158/0008-5472.CAN-07-5870.
Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K, Cross D, Tan LK, Tao J, Gopalakrishnan V, Tang BL, Kon OL, Tan P. Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res. 2008 Jun 15;68(12):4623–4630.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2008

Volume

68

Issue

12

Start / End Page

4623 / 4630

Location

United States

Related Subject Headings

  • rab GTP-Binding Proteins
  • Tumor Cells, Cultured
  • Tissue Array Analysis
  • Stomach Neoplasms
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis