Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma Journal Article
| Authors: | Rodić, N.; Steranka, J. P.; Makohon-Moore, A.; Moyer, A.; Shen, P.; Sharma, R.; Kohutek, Z. A.; Huang, C. R.; Ahn, D.; Mita, P.; Taylor, M. S.; Barker, N. J.; Hruban, R. H.; Iacobuzio-Donahue, C. A.; Boeke, J. D.; Burns, K. H. |
| Article Title: | Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma |
| 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. © 2015 Nature America, Inc. All rights reserved. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; aged; primary tumor; unclassified drug; cancer risk; polymerase chain reaction; gene targeting; protein; immunoreactivity; human genome; amplicon; pancreas adenocarcinoma; mutation rate; genetic risk; gene insertion; genomic dna; chromosome 9; open reading frame; chromosome 16; retroposon; clonal evolution; apoptotic protease activating factor 1; human; priority journal; article; open reading frame 1 protein |
| Journal Title: | Nature Medicine |
| Volume: | 21 |
| Issue: | 9 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-09-01 |
| Start Page: | 1060 |
| End Page: | 1064 |
| Language: | English |
| DOI: | 10.1038/nm.3919 |
| PROVIDER: | scopus |
| PUBMED: | 26259033 |
| PMCID: | PMC4775273 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
