Five genes from chromosomal band 8p22 are significantly down‐regulated in ovarian carcinoma

Pils, Dietmar; Horak, Peter; Gleiß, Andreas; Sax, Cornelia; Fabjani, Gerhild; Moebus, Volker; Zielinski, Christoph; Reinthaller, Alexander; Zeillinger, Robert; Krainer, Michael

doi:10.1002/cncr.21538

Cited by 98 publications

(105 citation statements)

References 51 publications

(45 reference statements)

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“…1b). In agreement with our results, low expression of ADP-ribosylation factor PSD3 has previously been linked with poor prognosis in ovarian carcinomas [33]. Interestingly elevated expression of LPL is a marker of poor prognosis in chronic lymphocytic leukemia conflicting with the present result for breasts cancer [34].…”

Section: Candidate Genessupporting

confidence: 92%

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

Thomassen

Tan

Kruse

2008

Breast Cancer Res Treat

114

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. Abstract Breast cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth whereas others are causal for the various steps of metastasis. In a fraction of tumors deregulation of the same genes might be caused by epigenetic modulations, point mutations or the influence of other genes. We have investigated the relation of gene expression and chromosomal position, using eight datasets including more than 1200 breast tumors, to identify chromosomal regions and candidate genes possibly causal for breast cancer metastasis. By use of ''Gene Set Enrichment Analysis'' we have ranked chromosomal regions according to their relation to metastasis. Overrepresentation analysis identified regions with increased expression for chromosome 1q41-42, 8q24, 12q14, 16q22, 16q24, 17q12-21.2, 17q21-23, 17q25, 20q11, and 20q13 among metastasizing tumors and reduced gene expression at 1p31-21, 8p22-21, and 14q24. By analysis of genes with extremely imbalanced expression in these regions we identified DIRAS3 at 1p31, PSD3, LPL, EPHX2 at 8p21-22, and FOS at 14q24 as candidate metastasis suppressor genes. Potential metastasis promoting genes includes RECQL4 at 8q24, PRMT7 at 16q22, GINS2 at 16q24, and AURKA at 20q13.

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Section: Candidate Genessupporting

confidence: 92%

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

Thomassen

Tan

Kruse

2008

Breast Cancer Res Treat

114

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“…Our recent study suggested that the reduction of MTUS1 expression may be associated with advanced oral tongue SCC [15]. The reduced expression of MTUS1 has also been observed in colon cancer, ovarian cancer and pancreatic cancer [14,16,17]. In this study, our expressional and sequence analyses on MTUS1 gene provide additional evidences to support that MTUS1 may be a tumor suppressor for HNSCC.…”

Section: Introductionsupporting

confidence: 68%

Genomic assessments of the frequent loss of heterozygosity region on 8p21.3∼p22 in head and neck squamous cell carcinoma

Pungpravat

Huang

et al. 2007

Cancer Genetics and Cytogenetics

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Most human cancers are characterized by genetic instabilities. Chromosomal aberrations include segments of allelic imbalance identifiable by loss of heterozygosity (LOH) at polymorphic loci, which may be used to implicate regions harboring tumor suppressor genes. Here we performed whole genome LOH profiling on over 40 human head and neck squamous cell carcinoma (HNSCC) cell lines. Several frequent LOH regions have been identified on chromosomal arms 3p, 4p, 4q, 5q, 8p, 9p, 10p, 11q, and 17p. A genomic region of ∼7 Mb located at 8p22-p21.3 exhibits the most frequent LOH (87.9%), which suggested that this region harbors important tumor suppressor gene(s). Mitochondrial tumor suppressor gene 1 (MTUS1) is a recently identified candidate tumor suppressor gene that resides in this region. Consistent down-regulation in expression was observed in HNSCC for MTUS1 as measured by real-time quantitative RT-PCR. Sequence analysis of MTUS1 gene in HNSCC revealed several important sequence variants in the exon regions of this gene. Thus, our results suggested that MTUS1 is one of the candidate tumor suppressor gene(s) reside in 8p22-p21.3 for HNSCC. The identification of these candidate genes will facilitate the understanding of tumorigenesis of HNSCC. Further studies are needed to functionally evaluate those candidate genes.

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“…14 In the current analysis of a larger cohort, we observed that patients who had tumors with TUSC3 promoter methylation had significantly shorter progression-free and overall survival rates, with a median progression-free survival of 11.1 months in the methylated group versus 24.6 months in the unmethylated group (Fig. 1G).…”

Section: Tusc3 Promoter Methylation Predicts Survival In Patients Witmentioning

confidence: 55%

“…Expression was relatively quantified using TaqMan probes specific for TUSC3 Hs00185147_m1 and b2- microglobulin Hs99999907_m1 (Applied Biosystems), as described elsewhere, 14,30 and was expressed in relative ratio units. All PCR reactions were performed in at least 3 independent experiments, and RT-negative and template-negative controls were included.…”

Section: Dna and Rna Isolationmentioning

confidence: 99%

Methylation status of TUSC3 is a prognostic factor in ovarian cancer

Pils

Horak

Vaňhara

et al. 2012

Cancer

Self Cite

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BACKGROUND. Current prognostic information in ovarian cancer is based on tumor stage, tumor grade, and postoperative tumor size. Reliable molecular prognostic markers are scarce. In this article, the authors describe epigenetic events in a frequently deleted region on chromosome 8p22 that influence the expression of tumor suppressor candidate 3 (TUSC3), a putative tumor suppressor gene in ovarian cancer. METHODS. Messenger RNA expression and promoter hypermethylation of TUSC3 were studied in ovarian cancer cell lines and in tumor samples from 2 large, independent ovarian cancer cohorts using polymerase chain reaction-based methods. RESULTS. The results indicated that TUSC3 expression is decreased significantly because of promoter methylation in malignant ovarian tumors compared with benign controls. Almost 33% of ovarian cancer samples had detectable TUSC3 promoter methylation. Furthermore, methylation status of the TUSC3 promoter had a significant and independent influence on progression-free and overall survival. CONCLUSIONS. TUSC3 hypermethylation predicted progression-free and overall survival in ovarian cancer. The current observations suggested a role for N-glycosylating events in ovarian cancer pathogenesis in general and identified the epigenetic silencing of TUSC3 as a prognostic factor in this disease. Cancer 2013;119:946-54. V C 2012 American Cancer Society.KEYWORDS: TUSC3, methylation, ovarian cancer, glycosylation, progression-free survival, overall survival, biomarker.. INTRODUCTIONEpithelial ovarian cancer is the most lethal gynecologic malignancy and the fourth most frequent cause of cancer-related death among women in industrialized countries. 1 Because >75% of women are diagnosed with advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stages III and IV), an early diagnosis presents 1 of the challenges of this disease. Patients with advanced ovarian cancer undergo intensive multimodal therapy consisting of cytoreductive surgery and (neo)adjuvant platinum-based and taxane-based chemotherapy. Regardless of the progress made in surgical and medical therapies over recent decades, the outcome for women with advanced ovarian cancer remains grim. Innovative, hypothesis-driven approaches to biomarker development remain essential even in the era of high-throughput sequencing and various omics. Studies of promoter methylation patterns in tumor suppressor genes have yielded several promising methylated biomarker candidates. [2][3][4] In contrast to a gene or protein expression analysis, methylation can easily be detected using polymerase chain reaction (PCR)-based methods in both tumor material and body fluids. [5][6][7] TUSC3 (tumor suppressor candidate 3), originally named N33, was identified as a potential tumor suppressor gene in prostate cancer 8,9 and is located on chromosome band 8p22. Known homozygous deletions of this region in pancreatic cell lines 10,11 and prostate cancer cell lines 12,13 contain no other cancer-related genes except TUSC3, although mutations of the T...

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Five genes from chromosomal band 8p22 are significantly down‐regulated in ovarian carcinoma

Cited by 98 publications

References 51 publications

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

Genomic assessments of the frequent loss of heterozygosity region on 8p21.3∼p22 in head and neck squamous cell carcinoma

Methylation status of TUSC3 is a prognostic factor in ovarian cancer

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