학술논문
Impact of rs12917 MGMT Polymorphism on [18 F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL)
Document Type
Original Paper
Author
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.
Source
Molecular Imaging and Biology. 21(6):1182-1191
Subject
Language
English
ISSN
1536-1632
1860-2002
1860-2002
Abstract
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-[18 F]fluoro-D-glucose positron emission tomography ([18 F]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.