Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma.
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 1), 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.
Lung
Hong Lok
HL
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.
Cheng
Yue
Y
Kumaran
Mande Kuppusamy
MK
Liu
Edison Tak-Bun
ET
Murakami
Yoshinori
Y
Chan
Cheuk Yu
CY
Yau
Wing Lung
WL
Ko
Josephine Mun Yee
JM
Stanbridge
Eric J
EJ
Lung
Maria Li
ML
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D005819:Genetic Markers; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins