<i>MGMT-</i>Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective of<i>IDH</i>Status and Chromosome 10q Deletion

Fontana, Laura; Tabano, Silvia; Bonaparte, Eleonora; Marfia, Giovanni; Pesenti, Chiara; Falcone, Rossella; Augello, Claudia; Carlessi, Nicole; Silipigni, Rosamaria; Guerneri, Silvana; Campanella, Rolando; Caroli, Manuela; Sirchia, Silvia Maria; Bòsari, Silvano; Miozzo, Monica

doi:10.1093/jnen/nlw052

Cited by 20 publications

(25 citation statements)

References 41 publications

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“…Until last year, diffuse gliomas were classified on the basis of histological criteria and 2007 World Health Organization (WHO) grading [ 2 ]. The increasing and extensive characterization of the genomic landscape of gliomas prompted the identification of genetic and epigenetic markers useful for tumor molecular classification; in the future, these molecular signatures could also represent actionable targets in gliomas, as is already the case for other cancers [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry-based assay for the molecular diagnosis of glioma: concomitant detection of chromosome 1p/19q codeletion, and IDH1, IDH2, and TERT mutation status

et al. 2017

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The World Health Organization recently revised the diagnosis of glioma, to integrate molecular parameters, including IDH mutations and codeletion (loss of heterozygosity; LOH) of chromosome arms 1p/19q, into the definitions of adult glioma histological subtypes. Mutations in the TERT promoter may also be useful for glioma diagnosis and prognosis. The integration of molecular markers into routine diagnosis requires their rapid and reliable assessment. We propose a MassARRAY (MS)-based test that can identify 1p/19q codeletion using quantitative SNP genotyping and, simultaneously, characterize hotspot mutations in the IDH1, IDH2, and TERT genes in tumor DNA. We determined the reliability of the MS approach testing 50 gliomas and comparing the MS results with those obtained by standard methods, such as short tandem repeat genotyping, array comparative genomic hybridization (array-CGH) and Fluorescence In Situ Hybridization (FISH) for 1p/19q codeletion and Sanger sequencing for hotspots mutations. The results indicate that MS is suitable for the accurate, rapid, and cost-effective evaluation of chromosome deletions combined with hotspot mutation detection. This MS approach could be similarly exploited in evaluation of LOH in other situations of clinical and/or research importance.

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Section: Introductionmentioning

confidence: 99%

Mass spectrometry-based assay for the molecular diagnosis of glioma: concomitant detection of chromosome 1p/19q codeletion, and IDH1, IDH2, and TERT mutation status

et al. 2017

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“…Finally, another study found no influence of 10q LOH over OS independently of MGMT methylation status, but it was performed on a cohort of mix GBM and low grade gliomas. 40 We observed no PFS differences (P = .79) between group 1 and group 2, probably due to the fact that the majority of patients had tumor progression within the first 8 months of follow-up. This lack of association can also be explained by the inherent difficulties of determination of true tumor progression, distinguished from pseudoprogression and radionecrosis.…”

Section: Univariate Analysismentioning

confidence: 56%

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

et al. 2020

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Background Epigenetic inactivation of O6‐methylguanine‐methyltransferase (MGMT) gene by methylation of its promoter is predictive of Temozolomid (TMZ) response in glioblastoma (GBM). MGMT is located on chromosome 10q26 and the loss of chromosome 10q is observed in 70% of GBMs. In this study, we assessed the hypothesis that the dual inactivation of MGMT, by hypermethylation of MGMT promoter and by loss the long arm of chromosome 10 (10q), may confer greater sensitivity to TMZ. Methods A total of 149 tumor samples from patients diagnosed with GBM based on the WHO 2016 classification were included in this retrospective study between November 2016 and December 2018. Methylation status of MGMT promoter was evaluated by pyrosequencing and status of chromosome 10q was assessed by array comparative genomic hybridization. Results Glioblastoma patients with chromosome 10q loss associated with hypermethylation of MGMT promoter had significantly longer overall survival (OS) (P = .0024) and progression‐free survival (PFS) (P = .031). Indeed, median OS of patients with dual inactivation of MGMT was 21.5 months compared to 12 months and 8.1 months for groups with single MGMT inactivation by hypermethylation and by 10q loss, respectively. The group with no MGMT inactivation had 9.5 months OS. Moreover, all long‐term survivors with persistent response to TMZ treatment (OS ≥ 30 months) displayed dual inactivation of MGMT. Conclusions Our data suggest that the molecular subgroup characterized by the dual inactivation of MGMT receives greater benefit from TMZ treatment. The results of our study may be of immediate clinical interest since chromosome 10q status and methylation of MGMT promoter are commonly determined in routine practice.

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“…However, current comprehensive treatments, comprising surgery, radiotherapy, and chemotherapy, have not achieved the desired therapeutic effects [2,3]. With the continuous development of genomics, researchers are paying closer attention to the molecular expression changes of glioma patients, such as IDH status, MGMT promoter methylation, and 1p/19q codeletion [6,7]. Therefore, we explored biomarkers that could guide the early diagnosis, treatment, and prognosis of gliomas through genomic data.…”

Section: Introductionmentioning

confidence: 99%

PART1 and hsa-miR-429-Mediated SHCBP1 Expression Is an Independent Predictor of Poor Prognosis in Glioma Patients

Xuan¹,

Jin²,

Wang³

et al. 2020

BioMed Research International

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Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.

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MGMT-Methylated Alleles Are Distributed Heterogeneously Within Glioma Samples Irrespective ofIDHStatus and Chromosome 10q Deletion

Cited by 20 publications

References 41 publications

Mass spectrometry-based assay for the molecular diagnosis of glioma: concomitant detection of chromosome 1p/19q codeletion, and IDH1, IDH2, and TERT mutation status

Mass spectrometry-based assay for the molecular diagnosis of glioma: concomitant detection of chromosome 1p/19q codeletion, and IDH1, IDH2, and TERT mutation status

Dual MGMT inactivation by promoter hypermethylation and loss of the long arm of chromosome 10 in glioblastoma

PART1 and hsa-miR-429-Mediated SHCBP1 Expression Is an Independent Predictor of Poor Prognosis in Glioma Patients

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