Monochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma

Josephine M Y Ko, Ling Chan Pui, Lung Yau Wing, Kin Chan Ho, Chi Chan King, You Yu Zhuo, Mei Kwong Fung, Lance D. Miller, Edison T. Liu, Chun Yang Li, Paulisally H Y Lo, Eric J. Stanbridge, Cheuk On Tang, Gopesh Srivastava, Wah Tsao Sai, Simon Law, Maria Li Lung

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21 Citations (Scopus)


Loss of chromosome 13q regions in esophageal squamous cell carcinoma (ESCC) is a frequent event. Monochromosome transfer approaches provide direct functional evidence for tumor suppression by chromosome 13 in SLMT-1, an ESCC cell line, and identify critical regions at 13q12.3, 13q14.11, and 13q14.3. Differential gene expression profiles of three tumor-suppressing microcell hybrids (MCH) and their tumorigenic parental SLMT-1 cell line were revealed by competitive hybridization using 19k cDNA oligonucleotide microarrays. Nine candidate 13q14 tumor-suppressor genes (TSG), including RB1, showed down-regulation in SLMT-1, compared with NE1, an immortalized normal esophageal epithelial cell line; their average gene expression was restored in MCHs compared with SLMT-1. Reverse transcription-PCR validated gene expression levels in MCHs and a panel of ESCC cell lines. Results suggest that the tumor-suppressing effect is not attributed to RB1, but instead likely involves thrombospondin type I domain-containing 1 (THSD1), a novel candidate TSG mapping to 13q14. Quantitative reverse transcription-PCR detected down-regulation of THSD1 expression in 100% of ESCC and other cancer cell lines. Mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation, as analyzed by methylation-specific PCR and clonal bisulfite sequencing. Transfection of wild-type THSD1 into SLMT-1 resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth-suppressive activity. These findings suggest that THSD1 is a good candidate TSG.
Original languageEnglish
Pages (from-to)592-603
Number of pages12
JournalMolecular Cancer Research
Issue number4
Publication statusPublished - 1 Apr 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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