Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-09

AUTHORS

Nemanja Rodić, Jared P Steranka, Alvin Makohon-Moore, Allison Moyer, Peilin Shen, Reema Sharma, Zachary A Kohutek, Cheng Ran Huang, Daniel Ahn, Paolo Mita, Martin S Taylor, Norman J Barker, Ralph H Hruban, Christine A Iacobuzio-Donahue, Jef D Boeke, Kathleen H Burns

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms. More... »

PAGES

1060-1064

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.3919

DOI

http://dx.doi.org/10.1038/nm.3919

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046032787

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26259033


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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