title: Landscape of somatic retrotransposition in human cancers.
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.
authors: Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
authors: Eunjung
authors: E
authors: Lee
authors: Rebecca
authors: R
authors: Iskow
authors: Lixing
authors: L
authors: Yang
authors: Omer
authors: O
authors: Gokcumen
authors: Psalm
authors: P
authors: Haseley
authors: Lovelace J
authors: LJ
authors: Luquette
authors: Jens G
authors: JG
authors: Lohr
authors: Christopher C
authors: CC
authors: Harris
authors: Li
authors: L
authors: Ding
authors: Richard K
authors: RK
authors: Wilson
authors: David A
authors: DA
authors: Wheeler
authors: Richard A
authors: RA
authors: Gibbs
authors: Raju
authors: R
authors: Kucherlapati
authors: Charles
authors: C
authors: Lee
authors: Peter V
authors: PV
authors: Kharchenko
authors: Peter J
authors: PJ
authors: Park
mesh_terms: D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D015894:Genome, Human; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D053842:Microsatellite Instability; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D018626:Retroelements; D017422:Sequence Analysis, DNA
chemical_list: D018626:Retroelements