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

  • 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 KlugeEmail author
  • Martin S. StaegeEmail author
Research Article



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.


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.


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.


MGMT polymorphism rs12917 seems to affect chemotherapy response in PHL. The prognostic value of this polymorphism should be investigated in a larger patient cohort.

Key words

Pediatric Hodgkin lymphoma MGMT rs12917 [18F]FDG-PET qPET Deauville score 


Author Contributions

S.K.-H. and I.V. performed experiments; M.S.S. designed the research; S.K.-H., L.K., M.C., A.S., E.C., S.K., G.P., D.S., A.J.B., C.M.K., C.-O.S., B.E., W.-D.R., A.O., O.S., R.K., and M.S.S analyzed and discussed the data; S.K.-H., L.K., and M.S.S wrote the paper.

Funding Information

This work was supported by a fellowship from the Konrad-Adenauer-Stiftung (S.K.-H.).

Compliance with Ethical Standards

All patients and their guardians gave their written informed consent. The study was approved by the ethical committee of the Medical Faculty of the Martin Luther University Halle-Wittenberg.

Competing Interests

The authors declare that they have no competing interests.


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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  • Stefanie Kewitz-Hempel
    • 1
    • 2
    • 3
  • Lars Kurch
    • 4
  • Michaela Cepelova
    • 5
  • Ines Volkmer
    • 1
  • Axel Sauerbrey
    • 6
  • Elke Conrad
    • 7
  • Stephanie Knirsch
    • 8
  • Gabriele Pöpperl
    • 9
  • Daniel Steinbach
    • 10
  • Ambros J. Beer
    • 11
  • Christof M. Kramm
    • 1
    • 12
  • Carsten-Oliver Sahlmann
    • 13
  • Bernhard Erdlenbruch
    • 14
  • Wolf-Dieter Reinbold
    • 15
  • Andreas Odparlik
    • 16
  • Osama Sabri
    • 4
  • Regine Kluge
    • 4
    Email author
  • Martin S. Staege
    • 1
    Email author
  1. 1.Department of Pediatrics IMartin Luther University Halle-WittenbergHalleGermany
  2. 2.Department of Pediatric Hematology and OncologyJustus Liebig UniversityGiessenGermany
  3. 3.Department of Dermatology and VenereologyMartin Luther University Halle-WittenbergHalleGermany
  4. 4.Department of Nuclear MedicineUniversity Hospital of LeipzigLeipzigGermany
  5. 5.Department of Pediatric Hematology and Oncology, 2nd Faculty of MedicineCharles University in Prague and Motol University HospitalPrahaCzech Republic
  6. 6.Helios Childrens HospitalErfurtGermany
  7. 7.Department of Nuclear MedicineHelios Hospital ErfurtErfurtGermany
  8. 8.Pediatrics 5 (Oncology, Hematology, and Immunology)Klinikum Stuttgart, OlgahospitalStuttgartGermany
  9. 9.Department of Nuclear MedicineKlinikum Stuttgart, OlgahospitalStuttgartGermany
  10. 10.Department of Pediatric Hematology and OncologyUniversity Hospital UlmUlmGermany
  11. 11.Department of Nuclear MedicineUniversity HospitalUlmGermany
  12. 12.Division of Pediatric Hematology and OncologyUniversity Medical Center GöttingenGöttingenGermany
  13. 13.Department of Nuclear MedicineGeorg August UniversityGöttingenGermany
  14. 14.University Hospital for Children and AdolescentsJohannes Wesling Klinikum Minden, Ruhr University HospitalBochumGermany
  15. 15.Universitätsinstitut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin, Johannes Wesling Klinikum MindenRuhr University HospitalBochumGermany
  16. 16.Department of Nuclear MedicineMartin Luther University Halle-WittenbergHalleGermany

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