Posts Tagged ‘evpp0mg’

Landscape of somatic retrotransposition in human cancers. – PubMed – NCBI

Friday, May 27th, 2016

Landscape of somatic retrotransposition in human cancers 194 insertions in 43 WGS, mostly L1s w. ~50% near genes

Landscape of Somatic Retrotransposition in Human Cancers

Eunjung Lee1,2,
Rebecca Iskow3,
Lixing Yang1,
Omer Gokcumen3,
Psalm Haseley1,2,
Lovelace J. Luquette III1,
Jens G. Lohr4,5,
Christopher C. Harris6,
Li Ding6,
Richard K. Wilson6,
David A. Wheeler7,
Richard A. Gibbs7,
Raju Kucherlapati2,8,
Charles Lee3,
Peter V. Kharchenko1,9,*,
Peter J. Park1,2,9,*,
The Cancer Genome Atlas Research Network

Science 24 Aug 2012:
Vol. 337, Issue 6097, pp. 967-971
DOI: 10.1126/science.1222077

The paper describes the analysis of transposable elements (TE) insertions at single nucleotide resolution in 43 high coverage whole genome datasets from five cancer types. The authors developed a computational method that uses as input paired-end whole genome sequence data from tumor and normal sample aligned against a reference genome and a custom repeat assembly of TE sequences to detect the position and mechanism of TE insertion. The method identified 194 TE insertions (183 L1s, 10 Alus and 1 ERV). The diversity in the frequency of TE insertions in the same cancer type (ranging from 45-60 to 106 events per tumour) suggests the presence of tumour subtypes with respect to TE activity.

By intersecting the 194 TE with genome annotation, the authors found that 64 TE are in known genes (in UTRs and introns), most of which are implicated in tumour suppressor functions. Also, the TE events targeted genes that are frequently/recurrently mutated, suggesting that TE insertions can potentially contribute to cancer development. Gene expression analysis showed that TE insertion results in significantly decreasing the expression levels for the host gene. TE orientation also has an impact on the expression level, with antisense insertion being less disruptive.

Comparing the germline and somatic insertion sites shows notable differences. Germline L1s are significantly more depleted from genes compared to somatic L1s. Somatic L1s are significantly overrepresented within regions of DNA hypomethylation suggesting the DNA
hypomethylation promoted L1 integration.

Cell lineage analysis in human brain using endogenous retroelements. – PubMed – NCBI

Saturday, May 7th, 2016

Cell-lineage analysis in human #brain using endogenous retroelements Tracing L1 insertions w/ #singlecell sequencing

Using single cell WGS of 16 neuronal cells the authors investigated two somatic insertions of L1Hs elements in an adult human brain. Using these results the authors infer that L1 somatic insertions are infrequent and ALUs and SVAs somatic retrotransposition are extremely rare. Assessing two L1Hs insertions in 32 samples across different regions of this same adult brain, they found that while one insertion was spatially restricted (2x1cm region), the other was found across all samples of the adult brain (but not found in other tissues such as Heart, Lung, etc.). The more restricted one (L1Hs#1) is inferred to have happened during the Fetal stage (first trimester) while the broader one happened earlier, approximately 2 weeks
post-fertilization. Overall the paper is clear, concise, and simple. It answers an interesting biological question: Can retrotransposition be used as a marker of cell clonal expansion? It does, although the retrotransposition frequency is very small and SNVs might support better results for the same analysis due to their higher frequency..