Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma

Arthur Kwok Leung Cheung, Hong Lok Lung, Josephine Mun Yee Ko, Yue Cheng, Eric J. Stanbridge, Eugene R. Zabarovsky, John M. Nicholls, Daniel Chua, Sai Wah Tsao, Xin Yuan Guan, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

40 Citations (Scopus)


Chromosome 14 allelic loss is common in nasopharyngeal carcinoma (NPC) and may reflect essential tumor suppressor gene loss in tumorigenesis. An intact chromosome 14 was transferred to an NPC cell line using a microcell-mediated chromosome transfer approach. Microcell hybrids (MCHs) containing intact exogenously transferred chromosome 14 were tumor suppressive in athymic mice, demonstrating that intact chromosome 14 NPC MCHs are able to suppress tumor growth in mice. Comparative analysis of these MCHs and their derived tumor segregants identified 4 commonly eliminated tumor-suppressive CRs. Here we provide functional evidence that a gene, Mirror-Image POLydactyly 1 (MIPOL1), which maps within a single 14q13.1–13.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation. MIPOL1 gene expression is down-regulated in all NPC cell lines and in ≈63% of NPC tumors via promoter hypermethylation and allelic loss. SLC25A21 and FOXA1, 2 neighboring genes mapping to this region, did not show this frequent down-regulated gene expression or promoter hypermethylation, precluding possible global methylation effects and providing further evidence that MIPOL1 plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of MIPOL1 in the stable transfectants induces cell cycle arrest. MIPOL1 tumor suppression is related to up-regulation of the p21(WAF1/CIP1) and p27(KIP1) protein pathways. This study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development.
Original languageEnglish
Pages (from-to)14478-14483
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
Publication statusPublished - 25 Aug 2009

Scopus Subject Areas

  • General

User-Defined Keywords

  • Cell cycle arrest
  • Microcell-mediated chromosome transfer
  • MIPOL1
  • Promoter hypermethylation


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