Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance

So Mee Kwon, Shin-Hyuk Kang, Chul Kee Park, Shin Jung, Eun Sung Park, Ju Seog Lee, Se Hyuk Kim, Hyun Goo Woo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemnessrelated genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6) in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.

Original languageEnglish
Article numbere0140528
JournalPLoS One
Volume10
Issue number10
DOIs
Publication statusPublished - 2015 Oct 14

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drug resistance
Glioblastoma
Drug Resistance
Tumors
neoplasms
Pharmaceutical Preparations
Neoplasms
transcriptomics
Recurrence
Gene expression
gene expression
Neurons
Genes
neurons
Gene Expression
Gene Expression Profiling
DNA repair
resistance mechanisms
Glioma
DNA Repair

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance. / Kwon, So Mee; Kang, Shin-Hyuk; Park, Chul Kee; Jung, Shin; Park, Eun Sung; Lee, Ju Seog; Kim, Se Hyuk; Woo, Hyun Goo.

In: PLoS One, Vol. 10, No. 10, e0140528, 14.10.2015.

Research output: Contribution to journalArticle

Kwon, So Mee ; Kang, Shin-Hyuk ; Park, Chul Kee ; Jung, Shin ; Park, Eun Sung ; Lee, Ju Seog ; Kim, Se Hyuk ; Woo, Hyun Goo. / Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance. In: PLoS One. 2015 ; Vol. 10, No. 10.
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