The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

Bralten, Linda B.C.; Gravendeel, A.M.; Kloosterhof, Nanne K.; Sacchetti, Andrea; Vrijenhoek, Terry; Veltman, Joris A.; Bent, Martin J. van den; Kros, Johan M.; Hoogenraad, Casper C.; Smitt, Peter A.E. Sillevis; French, Pim J.

doi:10.1038/onc.2010.342

Cited by 28 publications

(28 citation statements)

References 43 publications

(58 reference statements)

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“…The CNTNAP2 gene also functions as a cell adhesion molecule and has been found to be either methylated or deleted in several different cancer types, e.g. glioma, myleoid leukemia, and pancreatic adenocarcinoma [43-45]. In the present study, elevated CNTNAP2 protein levels were prevalent in tumors from pN1 patients, but this association was not statistically significant likely due to the low number of events.…”

Section: Discussioncontrasting

confidence: 66%

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

et al. 2014

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BackgroundSquamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness.MethodsTo extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models.ResultsWe found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively.ConclusionsTaken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

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Section: Discussioncontrasting

confidence: 66%

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

et al. 2014

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“…CNTNAP2 , a member of the neurexin family of signaling and adhesion molecules, has been previously found to function as a tumor suppressor gene in gliomas 35 . Consistent with the potential pathogenic functions of the apparent CNTNAP2 rearrangements in rhabdoid tumors found in our analysis, CNTNAP2 has also been recently reported to be recurrently deleted in an independent cohort of rhabdoid tumor patients 18 .…”

Section: Resultsmentioning

confidence: 99%

“…1d). Additional mechanisms, including as of yet undetected mutations or silencing 35 , may contribute to the loss of CNTNAP2 expression in apparently non-rearranged cases (Fig. 1d).…”

Section: Resultsmentioning

confidence: 99%

PGBD5 promotes site-specific oncogenic mutations in human tumors

et al. 2017

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Genomic rearrangements are a hallmark of human cancers. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as an active DNA transposase expressed in the majority of childhood solid tumors, including lethal rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found previously undefined genomic rearrangements in human rhabdoid tumors. These rearrangements involved PGBD5-specific signal (PSS) sequences at their breakpoints, recurrently inactivating tumor suppressor genes. PGBD5 was physically associated with genomic PSS sequences that were also sufficient to mediate PGBD5-induced DNA rearrangements in rhabdoid tumor cells. Ectopic expression of PGBD5 in primary immortalized human cells was sufficient to promote cell transformation in vivo. This activity required specific catalytic residues in the PGBD5 transposase domain, as well as end-joining DNA repair, and induced structural rearrangements with PSS breakpoints. This defines PGBD5 as an oncogenic mutator and provides a plausible mechanism for site-specific DNA rearrangements in childhood and adult solid tumors.

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“…Among the 28 genes listed in Table 1, we further focused on 6 genes ( ADCY5 [20], [21], CNTNAP2 [22], [23], EVX1 [24], GFRA1 [25], PDE9A [26], [27] and TBX20 [28]) for which implications in transcription regulation, apoptosis or cell adhesion had been reported. Quantitative real-time RT-PCR analysis of these 6 genes was performed in 132 N and 151 T samples for which total RNA was available.…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation Profiles at Precancerous Stages Associated with Recurrence of Lung Adenocarcinoma

Sato

Arai²,

Kohno³

et al. 2013

PLoS ONE

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The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (ΔβT–N>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2′-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.

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The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

Cited by 28 publications

References 43 publications

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

PGBD5 promotes site-specific oncogenic mutations in human tumors

DNA Methylation Profiles at Precancerous Stages Associated with Recurrence of Lung Adenocarcinoma

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