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Expression of TSLC1 , a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation
Author(s) -
Ando Kiyohiro,
Ohira Miki,
Ozaki Toshinori,
Nakagawa Atsuko,
Akazawa Kohei,
Suenaga Yusuke,
Nakamura Yohko,
Koda Tadayuki,
Kamijo Takehiko,
Murakami Yoshinori,
Nakagawara Akira
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23776
Subject(s) - neuroblastoma , loss of heterozygosity , biology , tumor suppressor gene , cancer research , dna methylation , comparative genomic hybridization , microbiology and biotechnology , carcinogenesis , cancer , gene , gene expression , genetics , chromosome , cell culture , allele
Although it has been well documented that loss of human chromosome 11q is frequently observed in primary neuroblastomas, the smallest region of overlap (SRO) has not yet been precisely identified. Previously, we performed array‐comparative genomic hybridization (array‐CGH) analysis for 236 primary neuroblastomas to search for genomic aberrations with high‐resolution. In our study, we have identified the SRO of deletion (10‐Mb or less) at 11q23. Within this region, there exists a TSLC1/IGSF4/CADM1 gene ( Tumor suppressor in lung cancer 1/Immunoglobulin superfamily 4/Cell adhesion molecule 1 ), which has been identified as a putative tumor suppressor gene for lung and some other cancers. Consistent with previous observations, we have found that 35% of primary neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to other cancers, we could not detect the hypermethylation in its promoter region in primary neuroblastomas as well as neuroblastoma‐derived cell lines. The clinicopathological analysis demonstrated that TSLC1 expression levels significantly correlate with stage, Shimada's pathological classification, MYCN amplification status, TrkA expression levels and DNA index in primary neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels of TSLC1 were significantly associated with a poor prognosis in 108 patients with neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human neuroblastoma SH‐SY5Y cells. Collectively, our present findings suggest that TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma. © 2008 Wiley‐Liss, Inc.