{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:21:22Z","timestamp":1781104882166,"version":"3.54.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,25]]},"abstract":"<jats:p>\n                    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,\n                    <jats:italic>Mirror-Image POLydactyly 1 (MIPOL1)<\/jats:italic>\n                    , which maps within a single 14q13.1\u201313.3 CR and that hitherto has been reported to be associated only with a developmental disorder, specifically suppresses in vivo tumor formation.\n                    <jats:italic>MIPOL1<\/jats:italic>\n                    gene expression is down-regulated in all NPC cell lines and in \u224863% of NPC tumors via promoter hypermethylation and allelic loss.\n                    <jats:italic>SLC25A21<\/jats:italic>\n                    and\n                    <jats:italic>FOXA1<\/jats:italic>\n                    , 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\n                    <jats:italic>MIPOL1<\/jats:italic>\n                    plays a unique role in NPC. The protein localizes mainly to the nucleus. Re-expression of\n                    <jats:italic>MIPOL1<\/jats:italic>\n                    in the stable transfectants induces cell cycle arrest.\n                    <jats:italic>MIPOL1<\/jats:italic>\n                    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,\n                    <jats:italic>MIPOL1<\/jats:italic>\n                    , is associated with tumor development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900198106","type":"journal-article","created":{"date-parts":[[2009,8,10]],"date-time":"2009-08-10T21:28:49Z","timestamp":1249939729000},"page":"14478-14483","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene,\n                    <i>Mirror image polydactyly 1<\/i>\n                    , in nasopharyngeal carcinoma"],"prefix":"10.1073","volume":"106","author":[{"given":"Arthur Kwok Leung","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Lok","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine Mun Yee","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China;"},{"name":"Department of Biology, City of Hope, Beckman Research Institute, Duarte,CA 91010;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Stanbridge","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene R.","family":"Zabarovsky","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Departments of fPathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Wah","family":"Tsao","sequence":"additional","affiliation":[{"name":"Anatomy, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yuan","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Li","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People's Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,8,25]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"3348","article-title":"High resolution allelotype of microdissected primary nasopharyngeal carcinoma","volume":"60","author":"Lo KW","year":"2000","unstructured":"KW Lo, et al., High resolution allelotype of microdissected primary nasopharyngeal carcinoma. 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