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Impact of rs12917 MGMT Polymorphism on [18F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL)
S. Kewitz-Hempel, L. Kurch, M. Cepelova, I. Volkmer, A. Sauerbrey, E. Conrad, S. Knirsch, G. Pöpperl, D. Steinbach, AJ. Beer, CM. Kramm, CO. Sahlmann, B. Erdlenbruch, WD. Reinbold, A. Odparlik, O. Sabri, R. Kluge, MS. Staege,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
ProQuest Central
od 2005-01-01 do 2019-01-31
Medline Complete (EBSCOhost)
od 2011-02-01 do Před 1 rokem
Nursing & Allied Health Database (ProQuest)
od 2005-01-01 do 2019-01-31
Health & Medicine (ProQuest)
od 2005-01-01 do 2019-01-31
- MeSH
- dítě MeSH
- DNA modifikační methylasy genetika MeSH
- enzymy opravy DNA genetika MeSH
- fluorodeoxyglukosa F18 chemie MeSH
- Hodgkinova nemoc diagnostické zobrazování genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- mladiství MeSH
- nádorové buněčné linie MeSH
- nádorové supresorové proteiny genetika MeSH
- pozitronová emisní tomografie * MeSH
- předškolní dítě MeSH
- sekvence nukleotidů MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Department of Nuclear Medicine Georg August University Göttingen Germany
Department of Nuclear Medicine Helios Hospital Erfurt Erfurt Germany
Department of Nuclear Medicine Klinikum Stuttgart Olgahospital Stuttgart Germany
Department of Nuclear Medicine Martin Luther University Halle Wittenberg Halle Germany
Department of Nuclear Medicine University Hospital of Leipzig 04103 Leipzig Germany
Department of Nuclear Medicine University Hospital Ulm Germany
Department of Pediatric Hematology and Oncology University Hospital Ulm Ulm Germany
Helios Childrens Hospital Erfurt Germany
Pediatrics 5 Klinikum Stuttgart Olgahospital Stuttgart Germany
Citace poskytuje Crossref.org
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- $a Kewitz-Hempel, Stefanie $u Department of Pediatrics I, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle, Germany. Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany. Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle, Germany.
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