Tumor suppressive role of a 2.4 Mb 9q33-q34 critical region and DEC1 in esophageal squamous cell carcinoma

Lichun Yang, Alfred C.C. Leung, Josephine M.Y. Ko, Paulisally H.Y. Lo, Cheuk On Tang, Gopesh Srivastava, Mitsuo Oshimura, Eric J. Stanbridge, Yataro Daigo, Yusuke Nakamura, Cecilia M.C. Tang, Kwok W. Lau, Simon Law, Maria L. Lung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

41 Citations (Scopus)

Abstract

The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.
Original languageEnglish
Pages (from-to)697-705
Number of pages9
JournalOncogene
Volume24
Issue number4
DOIs
Publication statusPublished - 20 Jan 2005

Keywords

  • Chromosome 9
  • Deleted in esophageal cancer 1
  • Esophageal carcinoma
  • Microcell-mediated chromosome transfer
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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