<p>The impact of adjuvant radiotherapy on molecular prognostic markers in gliomas</p>

Abstract

Purpose Changes in MGMT promoter methylation, IDH1 and IDH2 mutation, and 1p/19q co-deletion status in gliomas between first and subsequent resections and their associated clinical factors are poorly described. In this study, we assayed these biomarkers in the clinical setting. Patients and methods We used multiplex ligation-dependent probe amplification to measure MGMT promoter methylation, IDH mutation status, and 1p/19q co-deletion in 45 paired tumor samples from patients undergoing resection and subsequent re-resections for gliomas. Results Molecular changes were present in 20 patients (44%). At least one molecular characteristic changed over time in 89% of patients with primary grade III tumors. Gliomas with IDH wild-type and/or non-co-deleted were stable, but IDH1 / 2 mutation and/or co-deletion were sometimes lost at the time of recurrence. In a multivariate analysis, adjuvant radiotherapy alone was independently associated ( P =0.02) with changes in molecular profile. Conclusion Molecular biomarkers change in gliomas during the course of the disease, most often MGMT methylation status. These changes in genetic profiles are related to adjuvant treatment with radiotherapy alone, which might be important for individualized treatment planning over the disease course.

Changes of O6-Methylguanine DNA Methyltransferase (MGMT) Promoter Methylation in Glioblastoma Relapse—A Meta-Analysis Type Literature Review

“…A couple of them were anecdotal or incidental because they had their main focus on other topics [39][40][41][42][43][44]. Others investigated larger patient cohorts to evaluate, whether the re-determination of the MGMT-methylation status in the relapse situation might be of clinical relevance [36,[45][46][47][48][49][50][51][52][53][54]. Different methods for measuring MGMT methylation and diverse selection criteria have been utilized in these reports ( Table 2).…”

“…The most recent publication on this topic reports patients with astrocytic tumors of different WHO grading [53]. Thus, 12 changes in MGMT promoter methylation status could be observed by MS-MLPA.…”

“…Main limitations of such a combined analysis are the inhomogeneity of cut-off values, selection criteria, utilized methods, and a potential positive publication bias. Additionally, 4 of the included studies analyzed not only GBM but also LGG [39,40,53,54]. Therefore, the limitation of our analysis derives from such limitations of the original studies.…”

Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

“…With regards to clinical heterogeneity, only 20.5% (9/44) of our enrolled articles mentioned the presence or absence of preoperative treatment [38,40,41,45,47,50,53,55]. Some studies suggested that both radiotherapy and chemotherapy can alter a patient's DNA methylation status; therefore, the type of preoperative treatment performed should be clari ed [83,84]. Moreover, four studies investigated the relationship between RASSF1A hypermethylation in peripheral blood and the risk of HCC, and the diagnosis of HCC was con rmed by imaging techniques and serum AFP levels, rather than through pathological examination [56][57][58][59].…”

Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

“…Glioblastoma (GBM) is the most malignant type of glioma, characterized by a high level of infiltration, therapeutic resistance, and poor prognosis with a modest median survival of 14.2 months, even under radiation plus temozolomide therapy (1). Genetic changes, including isocitrate dehydrogenase (IDH) 1/2 mutation, 1p/19q codeletion, and O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation have recently been accepted as crucial molecular characteristics for prognosis prediction and subgroup stratification (2)(3)(4). Besides these genetic modifications, overexpression of oncogenic protein-coding genes and non-coding RNAs (ncRNAs) (5) and dysregulated posttranslational modification (6) can also modulate the malignant phenotype of glioma.…”