In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 2966A-2966A
Abstract:
Human endogenous retrovirus (HERV) is a member of LTR-retrotransposon family. Retroviral invasions are thought to have occurred in the germ cell lines of human or human ancestors, and the fixed retroviral elements are recognized as HERV. A complete HERV sequence contains two long terminal repeats (LTRs) located at both ends. Because intact LTRs possess the highly conserved transcriptional promoter- and enhancer-sequences, to investigate insertional variations of HERV is a key process for understanding the etiology of human genetic diseases that remain unclear with the analyses targeting single nucleotide variations. However, genome-wide investigation of repetitive sequences including HERV is methodologically difficult, and comprehensive understanding of insertional variations of HERV, including a somatic retrotransposition of HERV, remains poor. In the previous study, we have identified two novel insertional polymorphisms of solo LTRs using the inverse PCR and cloning methods, and one of them was involved with the susceptibility to lung adenocarcinoma. Here, we detected multiple novel LTR loci in the human cancer tissues by developing the high-throughput sequencing method combined with inverse PCR. In this system, to preferentially detect insertional variations, primer sequences were designed based on the conserved region of the LTRs which have an identical sequence to the mate within the same HML-2 proviruse, because almost of known HERV insertional polymorphisms are found in HML-2, which is thought to be the most recently endogenized element of HERV, and the presence of an identical LTR sequence at both ends is necessary for the retrotransposition of exogenous retrovirus. The sequence reads generated from the high-throughput sequencer were trimmed, and the fragments consistent with the inverse PCR process were selected. Following the mapping to the reference genome, the sites not corresponding to known LTR loci were sorted out and subjected to the filtration to exclude the artificial fragments. As the result, some candidates of novel LTR loci were detected, and several of them were verified to be actually present both in tumor and non-tumor genomes using the Sanger method, suggesting they are insertional polymorphisms. By using this detection system, we are now challenging to investigate a novel LTR site specifically detected in tumor genome. Citation Format: Tomoaki Kahyo, Hidetaka Yamada, Hong Tao, Yusuke Inoue, Nobuya Kurabe, Haruhiko Sugimura. A comprehensive investigation of insertional variations of human endogenous retrovirus elements in tumor tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2966A. doi:10.1158/1538-7445.AM2015-2966A
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-2966A
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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