TY  - JOUR
A1  - Schauer, Stephanie N.
A1  - Carreira, Patricia E.
A1  - Shukla, Ruchi
A1  - Gerhardt, Daniel J.
A1  - Gerdes, Patricia
A1  - Sanchez-Luque, Francisco J.
A1  - Nicoli, Paola
A1  - Kindlova, Michaela
A1  - Ghisletti, Serena
A1  - Santos, Alexandre Dos
A1  - Rapoud, Delphine
A1  - Samuel, Didier
A1  - Faivre, Jamila
A1  - Ewing, Adam D.
A1  - Richardson, Sandra R.
A1  - Faulkner, Geoffrey J.
T1  - L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis
Y1  - 2018/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 639 
EP  - 653 
DO  - 10.1101/gr.226993.117 
VL  - 28 
IS  - 5 
UR  - http://genome.cshlp.org/content/28/5/639.abstract 
N2  - The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2)−/− mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including TF subfamily elements, and one GF subfamily example. One of the TF insertions carried a 3′ transduction, allowing us to identify its donor L1 and to demonstrate that this full-length TF element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors. 
ER  -