Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia

Galusca, Bogdan; Dumollard, Jean Marc; Lassandre, S.; Niveleau, Alain; Prades, J.‐M.; Estour, Bruno; Péoc’h, Michel

doi:10.1007/s00428-005-1268-5

Cited by 29 publications

(21 citation statements)

References 46 publications

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“…This phenomenon leads to abnormal expression of genes, especially those which promote cell survival and proliferation. Global DNA hypomethylation has been associated with the progression of lung cancer and has also been suggested as a potential complementary marker in differential diagnosis of thyroid neoplasia [65, 66]. In our study, transitional epithelium from adjacent non-cancerous tissue consistently showed a low level of methylation, comparable to the level of methylation in cancer tissue.…”

Section: Discussionsupporting

confidence: 59%

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer

Wojtczyk-Miaskowska

Presler

Michajłowski

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. Methods: To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. Results: The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). Conclusion: This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology.

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Section: Discussionsupporting

confidence: 59%

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer

Wojtczyk-Miaskowska

Presler

Michajłowski

et al. 2017

Cell Physiol Biochem

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“…These data reinforce the assumption that there is increased proliferation of mitochondria in Hürthle cell tumors associated with the overexpression of factors involved in mitochondrial biogenesis (Savagner et al 2003; Table 3). Global DNA methylation, using a monoclonal antibody specific for 5-methylcystidine (5-mc), was evaluated in a large series of thyroid tumors (including ten Hürthle cell FTA) and tumor-like lesions (Galusca et al 2005). The similar levels of 5-mc in FTA and in Hürthle cell FTA indicate that the global DNA methylation levels cannot be used to separate Hürthle from non-Hürthle cell tumors, but it would also be interesting to evaluate such levels in Hürthle cell FTC.…”

Section: R136mentioning

confidence: 99%

The biology and the genetics of Hürthle cell tumors of the thyroid

Máximo¹,

Lima²,

Prazeres³

et al. 2012

Endocrine-Related Cancer

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The biology and the genetics of Hü rthle cell tumors are reviewed starting from the characterization and differential diagnosis of the numerous benign and malignant, neoplastic and nonneoplastic lesions of the thyroid in which Hü rthle cell transformation is frequently observed. The clinicopathologic and molecular evidence obtained from the comparative study of the aforementioned conditions indicate that Hü rthle cell appearance represents a phenotype that is superimposed on the genotypic and conventional histopathologic features of the tumors. Hürthle cell tumors differ from their non-Hü rthle counterparts regarding the prevalence of large deletions of mitochondrial DNA (mtDNA), mutations of mtDNA genes coding for oxidative phosphorylation (OXPHOS) proteins (namely mutations of complex I subunit genes) and mutations of nuclear genes coding also for mitochondrial OXPHOS proteins. Such mitochondrial alterations lead to energy production defects in Hü rthle cell tumors; the increased proliferation of mitochondria may reflect a compensatory mechanism for such defects and is associated with the overexpression of factors involved in mitochondrial biogenesis. The mitochondrial abnormalities are also thought to play a major role in the predisposition for necrosis instead of apoptosis which seems to be blocked in most Hü rthle cell tumors. Finally, the results obtained in experimental models using cybrid cell lines and the data obtained from histopathologic and molecular studies of familial Hü rthle cell tumors are used, together with the aforementioned genetic and epigenetic alterations, to progress in the understanding of the mechanisms through which mitochondrial abnormalities may be involved in the different steps of thyroid carcinogenesis, from tumor initiation to metastization.

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“…global DNA methylation and global histone acetylation, in pre-neoplastic and neoplastic lesions of the prostate (8). Overall DNA methylation and global histone acetylation were investigated immunohistochemically also in oral squamous cell carcinoma and its precursors, thyroid neoplasia, lung cancer, and colon cancer (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). There are no data in the literature on the overall epigenetic status in PUNLMP.…”

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confidence: 99%

Immunohistochemical Evaluation of Global DNA Methylation and Histone Acetylation in Papillary Urothelial Neoplasm of Low Malignant Potential

Barbisan

Mazzucchelli

Santinelli

et al. 2008

Int J Immunopathol Pharmacol

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A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 nonrecurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.The 2004 WHO classification of the noninvasive papillary urothelial tumors subdivides the morphologic spectrum of the non-invasive urothelial papillary neoplasia into urothelial papilloma,

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Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia

Cited by 29 publications

References 46 publications

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer

The biology and the genetics of Hürthle cell tumors of the thyroid

Immunohistochemical Evaluation of Global DNA Methylation and Histone Acetylation in Papillary Urothelial Neoplasm of Low Malignant Potential

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