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Candidate Tumor-suppressor Gene (candidate + tumor-suppressor_gene)
Selected AbstractsMapping of nasopharyngeal carcinoma tumor-suppressive activity to a 1.8-megabase region of chromosome band 11q13GENES, CHROMOSOMES AND CANCER, Issue 1 2002Yue Cheng Nasopharyngeal carcinoma (NPC) is a malignancy that is particularly prevalent among populations from Southern China and Southeast Asian countries. Evidence for a genetic contribution to the disease has been documented, although the genetic basis for NPC development is not yet fully understood. Previous functional evidence of tumor-suppressive activity on chromosome band 11q13 in NPC was obtained using a microcell-mediated chromosome-transfer approach with HONE1 NPC cells. In the present study, this region was subjected to a detailed investigation of microcell hybrids and their tumor segregants using microsatellite analysis to narrow down the region of tumor-suppressive activity. Fluorescence in situ hybridization was also performed with BAC and cosmid probes to confirm the microsatellite data. The critical region responsible for tumor suppression was narrowed down to a 1.8-Mb interval, which does not tolerate an additional normal allele by chromosome transfer. One or two alleles from either endogenous or exogenous chromosomes at 11q13 were consistently eliminated during tumor growth. Results of this study suggest that a candidate tumor-suppressor gene, not the MEN1 gene, maps between D11S4907 and GSTP1 in NPC. © 2002 Wiley-Liss, Inc. [source] Reduced expression of MYO18B, a candidate tumor-suppressor gene on chromosome arm 22q, in ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Nozomu Yanaihara Abstract Allelic imbalance on chromosome arm 22q has been detected in 50,70% of ovarian cancers, suggesting the presence of a tumor-suppressor gene on this chromosome arm that is involved in ovarian carcinogenesis. Recently, we isolated a candidate tumor-suppressor gene, MYO18B, at 22q12.1, which is deleted, mutated and hypermethylated in approximately 50% of lung cancers. In our study, we analyzed genetic and epigenetic alterations of the MYO18B gene in ovarian cancers. Missense MYO18B mutations were detected in 1 of 4 (25%) ovarian cancer cell lines and in 1 of 17 (5.9%) primary ovarian cancers. MYO18B expression was reduced in all 4 ovarian cancer cell lines and in 12 of 17 (71%) of primary ovarian cancers. MYO18B expression was restored by treatment with 5-aza-2,-deoxycytidine and/or trichostatin A in 3 of 4 cell lines with reduced MYO18B expression, and hypermethylation of the promoter CpG island for MYO18B was observed in 2 of these 3 cell lines. Its hypermethylation was also observed in 2 of 15 (13%) primary ovarian cancers. Thus, it was indicated that MYO18B expression is reduced in a considerable fraction of ovarian cancers by several mechanisms, including hypermethylation, while the MYO18B gene is mutated in a small subset of ovarian cancers. The present results suggest that MYO18B alterations, including both epigenetic and genetic alterations, play an important role in ovarian carcinogenesis. © 2004 Wiley-Liss, Inc. [source] Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Dipok Kumar Dhar Abstract KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1 -expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley-Liss, Inc. [source] | ||||||||||