Landscape of somatic retrotransposition in human cancers.

TitleLandscape of somatic retrotransposition in human cancers.
Publication TypeJournal Article
Year of Publication2012
AuthorsLee, E, Iskow, R, Yang, L, Gokcumen, O, Haseley, P, Luquette, LJ, Lohr, JG, Harris, CC, Ding, L, Wilson, RK, Wheeler, DA, Gibbs, RA, Kucherlapati, R, Lee, C, Kharchenko, PV, Park, PJ
Corporate Authors
JournalScience
Volume337
Issue6097
Pagination967-71
Date Published2012 Aug 24
ISSN1095-9203
KeywordsBase Sequence, Cell Transformation, Neoplastic, Colorectal Neoplasms, DNA Methylation, Female, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Genome, Human, Glioblastoma, Humans, Long Interspersed Nucleotide Elements, Male, Microsatellite Instability, Molecular Sequence Annotation, Molecular Sequence Data, Multiple Myeloma, Mutagenesis, Insertional, Mutation, Ovarian Neoplasms, Prostatic Neoplasms, Retroelements, Sequence Analysis, DNA
Abstract

Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis.

DOI10.1126/science.1222077
Alternate JournalScience
PubMed ID22745252
PubMed Central IDPMC3656569
Grant ListF32 AG039979 / AG / NIA NIH HHS / United States
F32AG039979 / AG / NIA NIH HHS / United States
K25 AG037596 / AG / NIA NIH HHS / United States
K25AG037596 / AG / NIA NIH HHS / United States
R01 GM082798 / GM / NIGMS NIH HHS / United States
R01GM082798 / GM / NIGMS NIH HHS / United States
RC1HG005482 / HG / NHGRI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
U01 HG005725 / HG / NHGRI NIH HHS / United States
U01HG005209 / HG / NHGRI NIH HHS / United States
U01HG005725 / HG / NHGRI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24CA144025 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States