DNA methylation and related mechanisms inhibit LINE-1 (L1) expression, and hypomethylation of DNA allows the L1 retrotransposon “life cycle” to proceed.

<p>In normal somatic cells, DNA methylation and related mechanisms inhibit LINE-1 (L1) expression (left image). In neoplastic cells, hypomethylation of DNA allows the L1 retrotransposon “life cycle” to proceed (right image). Retrotransposition is shown in a simplified schematic under the red box as (from left to right) transcription, assembly of ORF1p and ORF2p with L1 RNA, and insertion of a new L1 sequence (L1′). Related tumor effects are conceptually shown as (i) somatic retrotransposition of L1 and nonautonomous repeat elements, such as <i>Alu</i> repeats; (ii) transcriptional changes induced by L1-encoded promoters (in antisense and sense) or impacts on area methylation; and (iii) L1 ORF2p-generated DNA breaks. ASP, L1 antisense promoter.</p

Repetitive sequences in the human genome.

<p>About half of our DNA bears homology to known classes of repeats (left chart). The largest class of repeats is the non-LTR retrotransposons, which consists mostly of LINE-1 (L1), L2, MIRs, and Alu elements (right chart). L2 and MIR sequences are not currently active, but subsets of L1 (17.88%), Alu (10.76%), and SVA sequences (not shown, 0.1%) are currently mobile in human genomes and are sources of genetic polymorphisms. Proportions were determined using a RepeatMasker (version rm-20110920, default settings, RepBase sequence database version 16.08) analysis of the Human February 2009 (GRCh37/hg19) assembly. LTR, long terminal repeat retrotransposons; L1, long interspersed element–1; L2, long interspersed element–2; MIR, mammalian wide interspersed repeat; <i>Alu</i>, a short interspersed element named for the <i>Alu</i>I restriction enzyme; SVA, a composite retrotransposon consisting of short interspersed repeat (SINE-R), variable number tandem repeat (VNTR), and <i>Alu</i> like sequence segments.</p

Additional file 2 of A map of mobile DNA insertions in the NCI-60 human cancer cell panel

A map of Alu insertion site positions in the NCI-60 cell panel. Genomic coordinates of TIP-chip peaks are provided. Reference insertions are indicated in column D (hg19), and known polymorphic variants are indicated by a ‘Y’ in column E (Y/N, yes/no). For each cell line in columns G-BN, a ‘1’ indicates that the insertion is present, while ‘0’ indicates that the insertion is not found. (XLSX 380 kb