Abstract A29: Searching for retrotransposon insertions from paired end sequencing of tumors
Authors: Ballinger Tracy J. , Ewing Adam 
Published: June 2012

The question of how active transposons are in tumors is a salient one because tumors are hypermethylated and stem-cell-like, two conditions under which transposons are active, and because there are many known cases of germline retrotransposon insertion polymorphisms leading to cancer [1]. While studies have shown that some retroelements are transcribed at higher levels in certain types of tumors [2], there are currently very few studies that have looked at somatic retrotransposon insertions in tumor genomes. Reactivation of transposable elements could be an alternate pathway to genomic instability, one of the defining properties of cancer, by increasing the rate of mutation via retrotransposon insertions. Indeed, Collier et. al. have proven this principle in mice using the Sleeping Beauty transposon, a reactivated ancient DNA transposon [3]. The characterization of somatic as well as germline polymorphic insertions will be important in the study of cancer, as it will provide insight into how active transposable elements are in tumors and what role they play in tumor formation.

The Cancer Genome Atlas project has generated paired-end whole-genome sequencing data of tumors and normal tissue from hundreds of cancer patients in order to detect mutations and, ultimately, develop personalized treatment for patients. We have applied a pipeline to detect insertion polymorphisms of LINE-1 and Alu elements in both patients' samples. The first step in the detection method is to filter out all discordant reads and map them to a library of consensus sequences for a specific retrotransposon family. Next, read pairs of reads that match a repeat element are mapped back to the reference genome. Lastly, the mapped reads are clustered based on their location in the reference genome, and insertion calls are made. Using this method we have found over four hundred new candidates for polymorphic insertions in seven patients, including some found only in the tumor samples.

While this study is in the preliminary stages, it will address the question of whether or to what degree retrotransposons are active in tumors by being able to detect an increase in the number of retrotransposons found in the tumor sample as compared to the normal tissue of the same patient. Furthermore, heritable polymorphic insertions can be linked to cancer if there are certain ones that are over-represented in cancer cohorts as compared to a normal population, such as those found in the 1000 Genomes project data. Including insertion mutations in the characterization of cancer genomes will contribute to better individualized treatment for patients.

1. Belancio et al. Genome Res. 2008;18(3):343–58.

2. Schulz. J Biomed Biotechnol. 2006;(1):836–72.

3. Collier et al. Nature. 2005;436(7048):272–76.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A29.