A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma

Xiaoyue Chen; Minjie Zhang; Haiyun Gan; Heping Wang; Jeong-Heon Lee; Dong Fang; Gaspar J. Kitange; Lihong He; Zeng Hu; Ian F. Parney; Fredric B. Meyer; Caterina Giannini; Jann N. Sarkaria; Zhiguo Zhang

doi:10.1038/s41467-018-05373-4

Nature Communications (Jul 2018)

A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma

Xiaoyue Chen,
Minjie Zhang,
Haiyun Gan,
Heping Wang,
Jeong-Heon Lee,
Dong Fang,
Gaspar J. Kitange,
Lihong He,
Zeng Hu,
Ian F. Parney,
Fredric B. Meyer,
Caterina Giannini,
Jann N. Sarkaria,
Zhiguo Zhang

Affiliations

Xiaoyue Chen: Biochemistry and Molecular Biology, Mayo Clinic
Minjie Zhang: Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Irving Cancer Research Center, Columbia University
Haiyun Gan: Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Irving Cancer Research Center, Columbia University
Heping Wang: Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Jeong-Heon Lee: Biochemistry and Molecular Biology, Mayo Clinic
Dong Fang: Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Irving Cancer Research Center, Columbia University
Gaspar J. Kitange: Department of Radiation Oncology, Mayo Clinic
Lihong He: Department of Radiation Oncology, Mayo Clinic
Zeng Hu: Department of Radiation Oncology, Mayo Clinic
Ian F. Parney: Department of Neurologic Surgery, Mayo Clinic
Fredric B. Meyer: Department of Neurologic Surgery, Mayo Clinic
Caterina Giannini: Department of Laboratory Medicine and Pathology, Mayo Clinic
Jann N. Sarkaria: Department of Radiation Oncology, Mayo Clinic
Zhiguo Zhang: Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Irving Cancer Research Center, Columbia University

DOI: https://doi.org/10.1038/s41467-018-05373-4
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 14

Abstract

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Temozolomide (TMZ) resistance in glioblastomas (GBM) is associated with increased MGMT expression. Here, the authors identify an enhancer between the promoters of MKI67 and MGMT, that when activated drives MGMT expression despite MGMT promoter methylation to confer TMZ resistance in GBM.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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