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Mob DNA. 2016 Nov 11;7:22. doi: 10.1186/s13100-016-0077-5. eCollection 2016.

Somatic retrotransposition is infrequent in glioblastomas.

Author information

1
Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD USA.
2
Department of Pathology, Johns Hopkins University School of Medicine, Miller Research Building (MRB) Room 447, 733 North Broadway, Baltimore, MD 21205 USA.
3
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Miller Research Building (MRB) Room 447, 733 North Broadway, Baltimore, MD 21205 USA.
4
Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY USA.
5
Institute for Systems Genetics, New York University Langone Medical Center, ACLSW Room 503, 430 East 29th Street, New York, NY 10016 USA.
6
Present address: Yale University, New Haven, CT USA.
7
Present address: L.E.K. Consulting, Boston, MA USA.
8
Present address: BioNTech AG, Mainz, Germany.
9
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA.
10
Present address: Mayo Clinic, Jacksonville, FL USA.
#
Contributed equally

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.

KEYWORDS:

Cancer; Glioblastoma; LINE-1; Retrotransposition

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