Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma

Ashida, Shingo; Nishimori, Isao; Tanimura, Masanobu; Onishi, Saburo; Shuin, Taro

doi:10.1007/s00432-002-0374-x

Cited by 54 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, aberrant methylation of CAIX has been demonstrated in renal cell carcinoma. [48][49][50] Supporting this, we also found indirect evidence for CAIX epigenetic regulation in this study with the re-expression of CAIX protein in the OVCA432 and UPN251 following chromatin modifying treatment with TSA.…”

Section: Discussionsupporting

confidence: 81%

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

Prencipe

McGoldrick²,

Perry³

et al. 2010

Cell Cycle

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 81%

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

Prencipe

McGoldrick²,

Perry³

et al. 2010

Cell Cycle

View full text Add to dashboard Cite

“…This finding explained overexpression of CA IX/CA XII in RCC. Further studies confirmed, at least for CA IX, that VHL mutations significantly correlate with CA9 expression in a series of RCC lines and that CA IX can identify early lesions in VHL kidneys [45,46] . Both CA IX and CA XII are subjected to pVHL control through HIF degradation also in normoxic tumor cells other than RCC and are induced in response to experimental as well as microenvironmental hypoxia [14,17] .…”

Section: Discussionmentioning

confidence: 87%

Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa

Kivelä

Parkkila²,

Saarnio³

et al. 2005

WJG

View full text Add to dashboard Cite

AIM:To analyze possible relationships between CA IX/ CA XII and pVHL expression in normal and neoplastic colorectal mucosa. METHODS:Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control. RESULTS:Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12 showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9 and CA12are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.

show abstract

“…The studies from which the data has been extracted (refs. 6-34) have all been checked to ensure that data published in multiple reports are not duplicated with some publications omitted for this reason (1,35,(48)(49)(50). Gene and protein locations have been renumbered where necessary according to GenBank sequence: AF010238 for genomic VHL and L15409 for mRNA, with A of the first initiator ATG being 1 and codon numbers in accordance with L15409.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Epigenetic Analysis of von Hippel-Lindau (VHL) Gene Alterations and Relationship with Clinical Variables in Sporadic Renal Cancer

Tirukonda²,

et al. 2006

View full text Add to dashboard Cite

Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumor suppressor gene are common in sporadic conventional renal cell carcinoma (cRCC). Further insight into the clinical significance of these changes may lead to increased biological understanding and identification of subgroups of patients differing prognostically or who may benefit from specific targeted treatments. We have comprehensively examined the VHL status in tissue samples from 115 patients undergoing nephrectomy, including 96 with sporadic cRCC. In patients with cRCC, loss of heterozygosity was found in 78.4%, mutation in 71%, and promoter methylation in 20.4% of samples. Multiplex ligation-dependent probe amplification identified intragenic copy number changes in several samples including two which were otherwise thought to be VHLnoninvolved. Overall, evidence of biallelic inactivation was found in 74.2% of patients with cRCC. Many of the mutations were novel and approximately two-thirds were potentially truncating. Examination of these and other published findings confirmed mutation hotspots affecting codons 117 and 164, and revealed a common region of mutation in codons 60 to 78. Gender-specific differences in methylation and mutation were seen, although not quite achieving statistical significance (P = 0.068 and 0.11), and a possible association between methylation and polymorphism was identified. No significant differences were seen between VHL subgroups with regard to clinicopathologic features including stage, grade, tumor size, cancer-free and overall survival, with the exception of a significant association between loss of heterozygosity and grade, although a possible trend for survival differences based on mutation location was apparent.

show abstract

Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma

Abstract: These findings indicate that VHL suppresses CA IX expression but has no conclusive effect on CA XII and XIV expressions in RCC. CA IX expression is also driven by the methylation status of the CA9 gene.

Cited by 54 publications

References 27 publications

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa

Genetic and Epigenetic Analysis of von Hippel-Lindau (VHL) Gene Alterations and Relationship with Clinical Variables in Sporadic Renal Cancer

Contact Info

Product

Resources

About