Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

Peters, Inga; Dubrowinskaja, Natalia; Kogosov, Michael; Abbas, Mahmoud; Hennenlotter, Jörg; Klot, Christoph von; Merseburger, Axel S.; Stenzl, Arnulf; Scherer, Ralph; Kuczyk, Markus A.; Serth, Jürgen

doi:10.1186/1471-2407-14-101

Cited by 10 publications

(6 citation statements)

References 14 publications

(20 reference statements)

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“…GATA4 has recently been implicated in childhood onset diabetes . GATA 5 CpG island hypermethylation in renal carcinoma appear to identify aggressive phenotypes with poor outcomes . In animal models, GATA6 has been shown to orchestrate cardiac muscle hypertrophy in response to pressure stress and increase hepcidin expression in inflammatory states .…”

Section: Introductionmentioning

confidence: 99%

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

et al. 2015

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Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature.

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Section: Introductionmentioning

confidence: 99%

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

et al. 2015

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“…Histopathologically, clear cell renal cell carcinoma (CCRCC) accounts for approximately 75% of newly diagnosed RCC cases. Papillary (10–15%), chromophobe (5%), and other rare forms account for the remainder [2–4]. RCC is heterogeneous in clinical behavior, tumors with similar grade and stage may behave differently, and the outcome of RCC differs significantly among patients [2,3,5].…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation of PCDH8 is a Potential Prognostic Biomarker for Patients with Clear Cell Renal Cell Carcinoma

Lin

Wang

et al. 2014

Med Sci Monit

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BackgroundPCDH8 is a tumor suppressor that regulates cell adhesin, proliferation, and migration. It is often inactivated by aberrant promoter methylation in several human cancers, including clear cell renal cell carcinoma (CCRCC). The clinical significance of PCDH8 methylation in CCRCC remains unclear. The aim of this study was to investigate the relationship between PCDH8 methylation and clinicopathological characteristics as well as outcome of patients with CCRCC.Material/MethodsThe methylation status of PCDH8 in 153 CCRCC tissues and 97 paired adjacent normal renal tissues were examined using methylation-specific PCR (MSP). Then the relationships between PCDH8 methylation and clinicopathological features as well as progression-free survival of CCRCC patients were evaluated.ResultsPCDH8 methylation was significantly more frequent in CCRCC tissues compared with normal renal tissues. Moreover, PCDH8 methylation was significantly correlated with advanced clinical stage (P=0.0141), higher grade (P=0.0190), and lymph node metastasis (P=0.0098). In addition, multivariate analysis showed that PCDH8 methylation was independently associated with poor progression-free survival (P=0.0316).ConclusionsPCDH8 methylation is a frequent event in CCRCC and is correlated with unfavorable clinicopathological features. Moreover, PCDH8 methylation may be a useful biomarker to predict the progression of CCRCC.

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“…Over-expression of GATA5 reduces colony formation, cell proliferation, migration, invasion and anchorage-independent growth in colorectal cancer cells (Hellebrekers et al 2009); decreased expression has been implicated in carcinogenesis in both gastric and renal cancer cell lines as well as in colorectal and invasive ductal breast cancer tissue specimens (Hellebrekers et al 2009; Peters et al 2014; Wang et al 2014). Inactivation of the likely tumor suppressor GATA5 by promoter methylation was previously reported in gastric and colorectal cell lines, gastric cancers and dysplasias (Akiyama et al 2003; Wang et al 2011; Wen et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and genetic variation in GATA5 is associated with gastric disease risk

et al. 2016

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Gastric cancer incidence varies considerably among populations, even those with comparable rates of Helicobacter pylori infection. To test the hypothesis that genetic variation plays a role in gastric disease, we assessed the relationship between genotypes and gastric histopathology in a Colombian study population, using a genotyping array of immune-related single nucleotide polymorphisms (SNPs). Two synonymous SNPs (rs6061243 and rs6587239) were associated with progression of premalignant gastric lesions in a dominant-effects model after correction for multiple comparisons (p = 2.63E–07 and p = 7.97E–07, respectively); effect sizes were β = −0.863 and β = −0.815, respectively, where β is an estimate of effect on histopathology scores, which ranged from 1 (normal) to 5 (dysplasia). In our replication cohort, a second Colombian population, both SNPs were associated with histopathology when additively modeled (β = −0.256, 95 % CI = −0.47, −0.039; and β = −0.239, 95 % CI = −0.45, −0.024), and rs6587239 was significantly associated in a dominant-effects model (β = −0.330, 95 % CI = −0.66, 0.00). Because promoter methylation of GATA5 has previously been associated with gastric cancer, we also tested for the association of methylation status with more advanced histopathology scores in our samples and found a significant relationship (p = 0.001). A multivariate regression model revealed that the effects of both the promoter methylation and the exonic SNPs in GATA5 were independent. A SNP-by-methylation interaction term was also significant. This interaction between GATA5 variants and GATA5 promoter methylation indicates that the association of either factor with gastric disease progression is modified by the other.

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Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

Cited by 10 publications

References 14 publications

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

Aberrant Methylation of PCDH8 is a Potential Prognostic Biomarker for Patients with Clear Cell Renal Cell Carcinoma

Epigenetic and genetic variation in GATA5 is associated with gastric disease risk

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