| Autor: |
Kewitz-Hempel, Stefanie, Kurch, Lars, Cepelova, Michaela, Volkmer, Ines, Sauerbrey, Axel, Conrad, Elke, Knirsch, Stephanie, Pöpperl, Gabriele, Steinbach, Daniel, Beer, Ambros J., Kramm, Christof M., Sahlmann, Carsten-Oliver, Erdlenbruch, Bernhard, Reinbold, Wolf-Dieter, Odparlik, Andreas, Sabri, Osama, Kluge, Regine, Staege, Martin S. |
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| Zdroj: |
Molecular Imaging & Biology; Dec2019, Vol. 21 Issue 6, p1182-1191, 10p |
| Abstrakt: |
Purpose: The enzyme O6-methylguanine-DNA methyltransferase (MGMT) is an important component of the DNA repair machinery. MGMT removes O6-methylguanine from the DNA by transferring the methyl group to a cysteine residue in its active site. Recently, we detected the single nucleotide polymorphism (SNP) rs12917 (C/T) in the MGMT sequence adjacent to the active site in Hodgkin lymphoma (HL) cell line KM-H2. We now investigated whether this SNP is also present in other HL cell lines and patient samples. Furthermore, we asked whether this SNP might have an impact on metabolic response in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET), and on overall treatment outcome based on follow-up intervals of at least 34 months.Procedures: We determined the frequency of this MGMT polymorphism in 5 HL cell lines and in 29 pediatric HL (PHL) patients. The patient cohort included 17 female and 12 male patients aged between 4 and 18 years. After characterization of the sequence, we tested a possible association between rs12917 and age, gender, Ann Arbor stage, treatment group, metabolic response following two courses of OEPA (vincristine, etoposide, prednisone, and doxorubicin) chemotherapy, radiotherapy indication, and relapse status.Results: We detected the minor T allele in four of five HL cell lines. 11/29 patients carried the minor T allele whereas 18/29 patients showed homozygosity for the major C allele. Interestingly, we observed significantly better metabolic response in PHL patients carrying the rs12917 C allele resulting in a lower frequency of radiotherapy indication.Conclusion: MGMT polymorphism rs12917 seems to affect chemotherapy response in PHL. The prognostic value of this polymorphism should be investigated in a larger patient cohort. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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