Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma

Hong Lok Lung, Yue Cheng, Mande Kuppusamy Kumaran, Edison Tak Bun Liu, Yoshinori Murakami, Cheuk Yu Chan, Wing Lung Yau, Josephine Mun Yee Ko, Eric J. Stanbridge, Maria Li Lung*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    39 Scopus citations

    Abstract

    Previous studies transferring an intact chromosome 11 into HONE1 cells demonstrated the functional significance of chromosome regions, 11q13 and 11q22-23, in nasopharyngeal carcinoma (NPC) development. In our study the 11q22-23 region was comprehensively re-investigated by detailed microsatellite and single nucleotide polymorphism genotyping and by fluorescence in situ hybridization to map precisely the regions containing tumor suppressive activity. We observed 3 chromosomal intervals within 11q22-23 that were commonly lost in the tumor segregants derived from HONE1/chromosome 11 hybrids. One critical region of 0.36 Mb was mapped near the marker D11S2000 and a second 0.44 Mb region was located around the markers D11S1300 and D11S1391. In a third region high allelic loss was also observed at marker D11S4484, where a newly cloned tumor suppressor gene, TSLC1 (tumor suppressor in lung cancer I), is located. The gene expression analysis showed absence or low expression levels of TSLC1 mRNA in 4 highly tumorigenic NPC cell lines. In addition, the methylation study results show that the TSLC1 promoter region was hypermethylated in all 4 NPC cell lines and re-expression of the gene occurs in HONE1 cells after 5-aza-2′-deoxycytidine treatment. Hence, the mode of silencing of this candidate TSG in NPC may be attributed to promoter hypermethylation. We have obtained functional evidence for multiple critical tumor suppressive regions in 11q22-23 by fine deletion mapping and for inactivation of TSLC1 being one of these candidate TSGs in NPC development.

    Original languageEnglish (US)
    Pages (from-to)628-635
    Number of pages8
    JournalInternational Journal of Cancer
    Volume112
    Issue number4
    DOIs
    StatePublished - Nov 20 2004

    Keywords

    • Chromosome 11q22-23
    • Chromosome mapping
    • Microcell hybrid
    • Nasopharyngeal carcinoma
    • TSLC1

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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