Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor ? tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction

Wijnhoven, Bas P. L.; Lindstedt, Eric Wim; Abbou, Mustaffa; IJzendoorn, Ynske; Krijger, Ronald R. de; Tilanus, Hugo W.; Dinjens, Winand N.M.

doi:10.1002/ijc.1559

Cited by 17 publications

(16 citation statements)

References 25 publications

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“…Previous research demonstrated that tumors carrying von Hippel‐Lindau (VHL) mutations causes the failure to bind and destabilize HIF‐1α 12 . In previous studies by our and other labs, no mutation of the VHL TSG was found in gastric cancer 13,14 . These results suggest an important link between genetic alterations of the SDHB gene and HIF‐α stabilization in gastric cancers in the absence of VHL mutations.…”

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confidence: 49%

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Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Cao

Song

Kang

et al. 2010

Pathology International

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Recently, the succinate dehydrogenase subunit B gene, SDHB, has emerged as a novel tumor suppressor. In this study, we have examined the genetic and epigenetic alterations of the SDHB gene in sporadic gastric adenocarcinomas in order to investigate if the SDHB gene is involved in gastric carcinogenesis. The expression of SDHB proteins was also examined with immunohistochemistry and Western blot in 184 and eight gastric cancers, respectively. There was loss or reduced expression of SDHB in 45 (24.5%) of the 184 gastric cancers. Statistically, altered expression of SDHB was not associated with clinicopathological parameters, including tumor differentiation, location, depth of invasion, and lymph node metastasis (P > 0.05). Western blot analysis showed a reduced expression of SDHB in four (50.0%) of the eight paired gastric cancer tissues. Genetic analysis showed one missense mutation, GCC --> ACC (Ala --> Thr) at codon 29. In addition, promoter hypermethylation was not detected in the gastric cancer samples. This is the first investigation of the genetic and protein expression analysis of the SDHB gene in gastric cancers. Our results suggest that genetic, epigenetic, and protein expression pattern alterations of the SDHB gene might play a minor role in the development or progression of gastric cancers.

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supporting

confidence: 49%

“…12 In previous studies by our and other labs, no mutation of the VHL TSG was found in gastric cancer. 13,14 These results suggest an important link between genetic alterations of the SDHB gene and HIF-a stabilization in gastric cancers in the absence of VHL mutations.…”

mentioning

confidence: 75%

Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Cao

Song

Kang

et al. 2010

Pathology International

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“…To screen the entire open reading frame of the VHL gene, including flanking 3′ and 5′ untranslated regions and all intron‐exon boundaries, we developed 9 primer sets resulting in amplicons of about 200 bp, as necessary for paraffin‐derived DNA samples. Primer pairs and PCR conditions were described previously 39. None of the primer pairs matched to amplify sequences of the processed pseudogene of the VHL gene located at 1q12 40.…”

Section: Methodsmentioning

confidence: 99%

“…LOH analyses were performed for tumors with VHL mutations when constitutional DNA of the same patient was available. Allelic imbalance of the VHL locus was examined at microsatellite loci D3S1110, D3S3525 and by PCR‐SSCP of the SNP 462262 and SNP 35668 loci as described previously 39. PCR amplification of tumor and normal DNA was performed essentially as described above for SSCP analysis.…”

Section: Methodsmentioning

confidence: 99%

Von Hippel‐Lindau gene alterations in sporadic benign and malignant pheochromocytomas

Dannenberg

Krijger

Harst

et al. 2003

Intl Journal of Cancer

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The Von Hippel-Lindau (VHL) gene product has a wide spectrum of tissue-specific functions, and specific germline mutations are associated with clinical phenotypes in VHL disease. In particular, missense mutations are correlated with the susceptibility to pheochromocytomas. An association between VHL aberrations and prognosis has been suggested in renal clear cell carcinoma but has not been studied in pheochromocytomas. We studied the frequency and spectrum of VHL alterations in apparently sporadic pheochromocytomas in relation to the clinical behavior in 72 patients, including 48 patients with clinically benign and 24 patients with malignant pheochromocytomas. Single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing, loss of heterozygosity analysis of the VHL locus and immunohistochemistry for VHL protein expression were used to investigate somatic VHL gene alterations. In 2 patients, 1 with a malignant tumor, germline mutations were identified in the stop codon. Tumor-specific intragenic VHL mutations and accompanying loss of heterozygosity were identified in 2 (4.3%) of 47 sporadic benign pheochromocyto- Key words: Von Hippel-Lindau; pheochromocytoma; mutation; loss of heterozygosityVon Hippel-Lindau (VHL) disease is characterized by the development of multiple highly vascularized tumors in mesenchymal and neural crest-derived tissues of several organ systems. These concern mostly the central nervous system (hemangioblastoma), eye (retinal angioma), kidney (renal clear cell carcinoma), adrenal medulla (pheochromocytoma), inner ear (endolymphatic sac tumor) and endocrine pancreas (islet cell tumors). 1 In nearly all VHL patients, germline mutations or deletions in the VHL gene can be identified. 2,3 The VHL gene codes for a 213-amino acid protein (pVHL), which is involved in regulation of angiogenesis, extracellular matrix formation and plays a role in the cell cycle. 4 -9 As a recessive tumor suppressor gene, VHL demonstrates some important additional features, such as allelic heterogeneity resulting in genotypephenotype correlations and epigenetic effects. 10 -12 A correlation has been found between the nature and localization of inactivating mutations and the clinical consequences in patients afflicted by VHL disease. In particular, the development of pheochromocytoma (PCC) in VHL disease (type II VHL disease) is strongly correlated with missense mutations. These are found in 96% of these families, frequently in the exon 3-encoded ␣-domain of pVHL. 10 -13 PCC may even be the only tumor arising in some individuals with VHL type II disease. It is hypothesized that some retention of pVHL function is necessary in the development of PCC, arising from a dominant-negative effect of mutated pVHL and based on its involvement in the VHL-Elongin C-Elongin B complex. 14 The majority of PCCs occur sporadically, and the genetic mechanisms underlying their tumorigenesis and progression towards malignancy are poorly understood. At present, one cannot predict which patient will experience progres...

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“…The prevalence of MSI, either MSI-H or "MSI-low," has been reported to be approximately 5% to 10%. 13,20,27,43 The frequency of MSI-H, however, has been reported inconsistently in BE-associated adenocarcinoma, 13,20,27,43 and little is known about the clinicopathologic and molecular features and the biological behavior of microsatellite unstable BE-associated adenocarcinoma. Thus, the aims of this study were to further clarify the frequency of MSI and to characterize BE-associated adenocarcinomas with or without MSI.…”

mentioning

confidence: 99%

Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma

Farris

Demicco²,

Le³

et al. 2011

American Journal of Surgical Pathology

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Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor ? tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction

Cited by 17 publications

References 25 publications

Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers

Von Hippel‐Lindau gene alterations in sporadic benign and malignant pheochromocytomas

Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma

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