Somatic retrotransposition is infrequent in glioblastomas

Pragathi Achanta, Jared P. Steranka, Zuojian Tang, Nemanja Rodić, Reema Sharma, Wan Rou Yang, Sisi Ma, Mark Grivainis, Cheng Ran Lisa Huang, Anna M. Schneider, Gary L. Gallia, Gregory J. Riggins, Alfredo Quinones-Hinojosa, David Fenyö, Jef D. Boeke, Kathleen H. Burns

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Gliomas are the most common primary brain tumors in adults. We sought to understand the roles of endogenous transposable elements in these malignancies by identifying evidence of somatic retrotransposition in glioblastomas (GBM). We performed transposon insertion profiling of the active subfamily of Long INterspersed Element-1 (LINE-1) elements by deep sequencing (TIPseq) on genomic DNA of low passage oncosphere cell lines derived from 7 primary GBM biopsies, 3 secondary GBM tissue samples, and matched normal intravenous blood samples from the same individuals. Results: We found and PCR validated one somatically acquired tumor-specific insertion in a case of secondary GBM. No LINE-1 insertions present in primary GBM oncosphere cultures were missing from corresponding blood samples. However, several copies of the element (11) were found in genomic DNA from blood and not in the oncosphere cultures. SNP 6.0 microarray analysis revealed deletions or loss of heterozygosity in the tumor genomes over the intervals corresponding to these LINE-1 insertions. Conclusions: These findings indicate that LINE-1 retrotransposon can act as an infrequent insertional mutagen in secondary GBM, but that retrotransposition is uncommon in these central nervous system tumors as compared to other neoplasias.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMobile DNA
Volume7
Issue number1
DOIs
StatePublished - Nov 11 2016

Bibliographical note

Funding Information:
This work was supported by the American Brain Tumor Association (ABTA, K.H.B.); a Burroughs Wellcome Fund Career Award for Biomedical Scientists Program (K.H.B.); US National Institutes of Health awards R01CA161210 (J.D.B.), R01CA163705 (K.H.B.) and R01GM103999 (K.H.B.), R01NS070024 (A.Q.-H), as well as the National Institute of General Medical Sciences Center for Systems Biology of Retrotransposition P50GM107632 (K.H.B. and J.D.B.).

Publisher Copyright:
© 2016 The Author(s).

Keywords

  • Cancer
  • Glioblastoma
  • LINE-1
  • Retrotransposition

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