MGMT promoter methylation in plasma of glioma patients receiving temozolomide

Fiano, Valentina; Trevisan, Morena; Trevisan, Elisa; Senetta, Rebecca; Castiglione, Anna; Sacerdote, Carlotta; Gillio-Tos, Anna; Marco, Laura De; Grasso, Chiara; Magistrello, Michela; Tondat, Fabrizio; Rudà, Roberta; Cassoni, Paola; Soffietti, Riccardo; Merletti, Franco

doi:10.1007/s11060-014-1395-4

Cited by 42 publications

(28 citation statements)

References 37 publications

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“…More recently, a meta-analysis of 10 eligible studies, including the MGMT methylation status of more than four thousand subjects, confirmed that patients bearing this genotype present longer overall survival (Binabaj et al, 2018), emphasizing MGMT status as an independent indicator of a favorable prognosis. MGMT methylation could also be found in patient serum and strongly correlated with its presence in the tumor tissues (Fiano et al, 2014), suggesting that detection in blood samples could represent a re-DNA repair genes in astrocytoma 3 liable tool to predict response to TMZ treatment. MGMT methylation also disclosed its relevance as biomarker for other types of malignancies, including breast (Neto et al, 2012), colorectal (Lee et al, 2009), prostate (Cortese et al, 2012), cervical , gastric (Jin et al, 2014) and lung (Ostrow et al, 2010) cancers.…”

Section: Dna Repair Genes As Biomarkers Of Astrocytoma Aggressivenessmentioning

confidence: 99%

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

et al. 2020

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Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, showing rapid development and resistance to therapies. On average, patients survive 14.6 months after diagnosis and less than 5% survive five years or more. Several pieces of evidence have suggested that the DNA damage signaling and repair activities are directly correlated with GBM phenotype and exhibit opposite functions in cancer establishment and progression. The functions of these pathways appear to present a dual role in tumorigenesis and cancer progression. Activation and/or overexpression of ATRX, ATM and RAD51 genes were extensively characterized as barriers for GBM initiation, but paradoxically the exacerbated activity of these genes was further associated with cancer progression to more aggressive stages. Excessive amounts of other DNA repair proteins, namely HJURP, EXO1, NEIL3, BRCA2, and BRIP, have also been connected to proliferative competence, resistance and poor prognosis. This scenario suggests that these networks help tumor cells to manage replicative stress and treatment-induced damage, diminishing genome instability and conferring therapy resistance. Finally, in this review we address promising new drugs and therapeutic approaches with potential to improve patient survival. However, despite all technological advances, the prognosis is still dismal and further research is needed to dissect such complex mechanisms.

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Section: Dna Repair Genes As Biomarkers Of Astrocytoma Aggressivenessmentioning

confidence: 99%

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

et al. 2020

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“…12 CD79B mutations were detected in 83.1% of PCNS-DLBCLs by Nakamura et al 13 Hypermethylation of the CpG islands in the promoter regions is an important mechanism for the silencing of tumor suppressor genes and DNA repair genes. Previous studies have revealed that the gene which encodes the DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) was transcriptionally silenced by promoter methylation in several human tumors, including gliomas, 14,15 systemic lymphomas 16 and PCNS-DLBCL. 17 The MGMT protein can repair the damaging effect of alkylating chemotherapy agents on the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Frequency of MYD88 and CD79B mutations, and MGMT methylation in primary central nervous system diffuse large B‐cell lymphoma

et al. 2017

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Primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) and systemic DLBCL harbor mutations in MYD88 and CD79B. DNA methyltransferase (MGMT) is methylated in some DLBCL. Our goal was to investigate the frequencies of these events, which have not been previously reported within the same series of patients with PCNS-DLBCL. Fifty-four cases of PCNS-DLBCL from two institutions were analyzed by Sanger sequencing for MYD88 and CD79B, and pyrosequencing for MGMT. MYD88 mutations were identified in 68.8% (35 of 51 cases), with L265P being the most frequent mutation. Mutations other than L265P were identified in 21.6% of cases, of which eight novel MYD88 mutations were identified. Of mutated cases, 17.6% had homozygous/hemizygous MYD88 mutations, which has not been previously reported in PCNS-DLBCL. CD79B mutations were found in six of 19 cases (31.6%), all in the Y196 mutation hotspot. MGMT methylation was observed in 37% (20 of 54 cases). There was no significant difference in median overall survival (OS) between the wild type and mutated MYD88 cases, or between methylated and unmethylated MGMT cases. However, a significant difference (P = 0.028) was noted in median OS between the wild type and mutated CD79B cases.

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“…Lavon et al . and further studies confirmed this possibility and also explored the correlations with outcome and longitudinal evolution during disease course . cfDNA methylation analysis has also been proposed for diagnostic purposes in gliomas using CDKN2A promoter methylation assessment .…”

Section: Circulating Cell‐free Nucleic Acids Analysismentioning

confidence: 82%

Review: Peering through a keyhole: liquid biopsy in primary and metastatic central nervous system tumours

Bertero

Siravegna

Rudà

et al. 2019

Neuropathology Appl Neurobio

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2019) Neuropathology and Applied Neurobiology 45, 655-670 Peering through a keyhole: liquid biopsy in primary and metastatic central nervous system tumours Tumour molecular profiling by liquid biopsy is being investigated for a wide range of research and clinical purposes. The possibility of repeatedly interrogating the tumour profile using minimally invasive procedures is helping to understand spatial and temporal tumour heterogeneity, and to shed a light on mechanisms of resistance to targeted therapies. Moreover, this approach has been already implemented in clinical practice to address specific decisions regarding patients' follow-up and therapeutic management. For central nervous system (CNS) tumours, molecular profiling is particularly relevant for the proper characterization of primary neoplasms, while CNS metastases can significantly diverge from primary disease or extra-CNS metastases, thus compelling a dedicated assessment. Based on these considerations, effective liquid biopsy tools for CNS tumours are highly warranted and a significant amount of data have been accrued over the last few years. These results have shown that liquid biopsy can provide clinically meaningful information about both primary and metastatic CNS tumours, but specific considerations must be taken into account, for example, when choosing the source of liquid biopsy. Nevertheless, this approach is especially attractive for CNS tumours, as repeated tumour sampling is not feasible. The aim of our review was to thoroughly report the state-of-the-art regarding the opportunities and challenges posed by liquid biopsy in both primary and secondary CNS tumours.

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MGMT promoter methylation in plasma of glioma patients receiving temozolomide

Cited by 42 publications

References 37 publications

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

Frequency of MYD88 and CD79B mutations, and MGMT methylation in primary central nervous system diffuse large B‐cell lymphoma

Review: Peering through a keyhole: liquid biopsy in primary and metastatic central nervous system tumours

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