title: Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32.
abstract: Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.
authors.affiliation: Department of Biology, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Josephine Mun Yee
authors.initials: JM
authors.lastname: Ko
authors.forename: Wing Lung
authors.initials: WL
authors.lastname: Yau
authors.forename: Pui Ling
authors.initials: PL
authors.lastname: Chan
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.forename: Lichun
authors.initials: L
authors.lastname: Yang
authors.forename: Paulisally H Y
authors.initials: PH
authors.lastname: Lo
authors.forename: Johnny C O
authors.initials: JC
authors.lastname: Tang
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D004938:Esophageal Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D009693:Nucleic Acid Hybridization; D014183:Transplantation, Heterologous