EBV Conference 2008 Guangzhou - Baylor College of Medicine

172 (RegID: 1054)
Kwok Leung Cheung
Institution: The Hong Kong University of Science and Technology
e-mail: boarthur@ust.hk
MONOCHROMOSOME TRANSFER OF AN INTACT CHROMOSOME 14 SUPPRESSES
TUMOR FORMATION IN NASOPHARYNGEAL CARCINOMA
Arthur Kwok Leung Cheung, Hong Lok Lung, Yue Cheng, Eric John Stanbridge, and Maria Li Lung
Posterabstract:
Extensive allelic losses occur on chromosome 14 in a number of human cancers, including
nasopharyngeal carcinoma (NPC). In our previous studies using a microcell-mediated chromosome
transfer (MMCT) approach, microcell hybrids (MCHs) were established after transfer of an intact human
chromosome 14 into the HONE1 NPC cell line. Uniform loss of a commonly eliminated region was
mapped by microsatellite typing and fluorescence in situ hybridization (FISH) BAC assays to
chromosome regions at 14q11.2-13.1 and 14q32.1. We concluded that hybrid selection and tumor growth
in vivo were associated with this selective genomic elimination. Selected genes mapping to these
eliminated regions are now the subject of current investigations. To obtain direct conclusive evidence that
these regions are indeed responsible for actual tumor suppression, in this current study, new MCH cell
lines were established after transfer of chromosome 14, which retained the intact chromosome, as
confirmed by microsatellite and FISH assays. These MCH cell lines are tumor-suppressive, when injected
into nude mice. After a latency period of 6-8 weeks, tumors reaching the size of around 900 mm3 formed
by weeks 8-9, as compared to the recipient HONE1 NPC cell line, which formed tumors of that size by
week 5. The increased latency period and decreased size and number of tumors formed in the animals,
after addition of the intact chromosome 14 to the HONE1 cells, indicate that a gene or genes present in the
transferred chromosome are able to functionally complement the defects present in the NPC cell line.
Tumor segregants (TSs) were established from these MCH cell lines after 12 weeks, which allow further
molecular genotyping to narrow down the region of interest that presumably is associated with tumor
suppression. These studies are ongoing and results indicate that chromosome 14 contains critical regions
associated with tumor suppression in NPC.
EBV Conference 2008 Guangzhou
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