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01-12-2019 | Hodgkin Lymphoma | Research Article

Impact of rs12917 MGMT Polymorphism on [¹⁸F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL)

Authors: Stefanie Kewitz-Hempel, Lars Kurch, Michaela Cepelova, Ines Volkmer, Axel Sauerbrey, Elke Conrad, Stephanie Knirsch, Gabriele Pöpperl, Daniel Steinbach, Ambros J. Beer, Christof M. Kramm, Carsten-Oliver Sahlmann, Bernhard Erdlenbruch, Wolf-Dieter Reinbold, Andreas Odparlik, Osama Sabri, Regine Kluge, Martin S. Staege

Published in: Molecular Imaging and Biology | Issue 6/2019

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-[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.

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Title: Impact of rs12917 MGMT Polymorphism on [18F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL)
Authors: Stefanie Kewitz-Hempel
Lars Kurch
Michaela Cepelova
Ines Volkmer
Axel Sauerbrey
Elke Conrad
Stephanie Knirsch
Gabriele Pöpperl
Daniel Steinbach
Ambros J. Beer
Christof M. Kramm
Carsten-Oliver Sahlmann
Bernhard Erdlenbruch
Wolf-Dieter Reinbold
Andreas Odparlik
Osama Sabri
Regine Kluge
Martin S. Staege
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keywords: Hodgkin Lymphoma
Radiotherapy
Cytostatic Therapy
Published in: Molecular Imaging and Biology / Issue 6/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01350-5

Keynote webinar | Spotlight on sleep in brain health

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Impact of rs12917 MGMT Polymorphism on [¹⁸F]FDG-PET Response in Pediatric Hodgkin Lymphoma (PHL)

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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