Somatic retrotransposition is infrequent in glioblastomas.

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

doi:10.1186/s13100-016-0077-5

Abstract

BackgroundGliomas 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.ResultsWe 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13100-016-0077-5) contains supplementary material, which is available to authorized users.

Highlights

Gliomas are the most common primary brain tumors in adults
Transposon insertion profiling We obtained seven primary GBM samples from patients 50–65 years old as well as peripheral blood draws from the same individuals
Primary tissue directly from these resections was available in sufficient quantity to assay directly for four cases. We digested these samples with restriction enzymes, ligated vectorette oligonucleotides to their ends, and selectively amplified Long INterspersed Element-1 (LINE-1) genomic insertion sites using vectorette PCR as previously described

Summary

Introduction

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). Glioblastomas (GBMs) are the most common malignant form of primary brain tumor in adults, and are typically fatal. These are histologically aggressive gliomas, categorized by the World Health Organization (WHO) as grade IV astrocytomas; they are hypercellular with frequent mitotic figures, vascular proliferation and pseudopalisading necrosis. Primary GBMs arise de novo, and usually present as advanced cancers in patients over 50 years old. These are characterized genetically by amplification of epidermal growth factor receptor (EGFR), loss of heterozygosity (LOH) on chromosomes 10q and 17p, and phosphatase and tensin homologue (PTEN) mutation. This class of tumors is characterized by mutations in isocitrate dehydrogenase 1 (IDH1) and p53 tumor suppressor genes as well PDGFA amplification [1, 2]

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