1. ¹Department of Biology, Hong Kong University of Science and Technology, Hong Kong, China
2. ²Department of Pathology, The University of Hong Kong, Hong Kong, China
3. ³Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China
4. ⁴Department of Biomedical Science, Tottori University, Tottori, Japan
5. ⁵Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA
6. ⁶Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
7. ⁷Department of Pathology, Tuen Mun Hospital, Hong Kong, China
8. ⁸Department of Surgery, Tuen Mun Hospital, Hong Kong, China
9. ⁹Department of Surgery, The University of Hong Kong, Hong Kong, China

Correspondence: ML Lung, Department of Biology, Hong Kong University of Science and Technology, Hong Kong, China. E-mail: bomaria@ust.hk

Received 29 July 2004; Revised 2 September 2004; Accepted 6 September 2004; Published online 6 December 2004.

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.