Validating a clinically based MS-MLPA threshold through comparison with Sanger sequencing in glioblastoma patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61383082%3A_____%2F25%3A00001510" target="_blank" >RIV/61383082:_____/25:00001510 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/25:10492816 RIV/00216208:11150/25:10492816 RIV/00179906:_____/25:10492816 RIV/00064165:_____/25:10492816 RIV/00023736:_____/25:00013782

Result on the web

<a href="https://pubmed.ncbi.nlm.nih.gov/39881389/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/39881389/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13148-025-01822-2" target="_blank" >10.1186/s13148-025-01822-2</a>

Result language

angličtina

Original language name

Validating a clinically based MS-MLPA threshold through comparison with Sanger sequencing in glioblastoma patients

Original language description

Background: Glioblastoma is the commonest malignant brain tumor and has a very poor prognosis. Reduced expression of the MGMT gene (10q26.3), influenced primarily by the methylation of two differentially methylated regions (DMR1 and DMR2), is associated with a good response to temozolomide treatment. However, suitable methods for detecting the methylation of the MGMT gene promoter and setting appropriate cutoff values are debated. Results: A cohort of 108 patients with histologically and genetically defined glioblastoma was retrospectively examined with methylation-specific Sanger sequencing (sSeq) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methods. The DMR2 region was methylated in 29% of samples, whereas DMR1 was methylated in 12% of samples. Methylation detected with the MS-MLPA method using probes MGMT_215, MGMT_190, and MGMT_124 from the ME012-A1 kit (located in DMR1 and DMR2) correlated with the methylation of the corresponding CpG dinucleotides detected with sSeq (p = 0.005 for probe MGMT_215; p < 0.001 for probe MGMT_190; p = 0.016 for probe MGMT_124). The threshold for methylation detection with the MS-MLPA method was calculated with a ROC curve analysis and principal components analysis of the data obtained with the MS-MLPA and sSeq methods, yielding a weighted value of 0.362. Thus, methylation of the MGMT gene promoter was confirmed in 36% of samples. These patients had statistically significantly better overall survival (p = 0.003). Conclusions: Our results show that the threshold for methylation detection with the MS-MLPA method determined here is useful from a diagnostic perspective because it allows the stratification of patients who will benefit from specific treatment protocols, including temozolomide. Detailed analysis of the MGMT gene promoter enables the more-precise and personalized treatment of patients with glioblastoma.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NU21-04-00100" target="_blank" >NU21-04-00100: Targeting genomic diversity in primary and recurrent gliomas for further understanding of brain tumor pathogenesis.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

CLINICAL EPIGENETICS

ISSN

1868-7075

e-ISSN

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Volume of the periodical

17

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

1-12

UT code for WoS article

001410783100001

EID of the result in the Scopus database

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