MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry

Autor: Kalthoum Tlili, N. Karmeni, Nadia Mama, Ali Saad, Mohamed Tahar Yacoubi, Saoussen Trabelsi, H. Krifa, M. Mokni, M. Haddaji Mastouri, Marwa Chourabi, Mohamed Ladib, D. H’mida Ben Brahim
Rok vydání: 2015
Předmět:
0301 basic medicine
Adult
Male
Cancer Research
Adolescent
medicine.medical_treatment
Bioinformatics
Polymerase Chain Reaction
Immunoenzyme Techniques
03 medical and health sciences
Young Adult
0302 clinical medicine
medicine
Biomarkers
Tumor
Humans
Promoter Regions
Genetic
neoplasms
Gene
DNA Modification Methylases
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Chemotherapy
Predictive marker
Temozolomide
Base Sequence
Retinoblastoma
business.industry
Tumor Suppressor Proteins
General Medicine
Methylation
DNA Methylation
Middle Aged
medicine.disease
Prognosis
digestive system diseases
Survival Rate
030104 developmental biology
DNA Repair Enzymes
Oncology
CpG site
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
business
Glioblastoma
Nucleic Acid Amplification Techniques
medicine.drug
Follow-Up Studies
Zdroj: Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 18(4)
ISSN: 1699-3055
Popis: The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival. In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.
Databáze: OpenAIRE
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