Distribution of somatic mutations associated with cancer in Human Endogenous Retrovirus (HERVs) element

Human Endogenous Retroviruses (HERVs) account for approximately 8% of the human genome. Recent studies have reported that HERV elements participate in the process of malignant transformation or promote tumor growth through insertional mutagenesis or via counteracting tumor immunosurveilance. However, the relationship between comprehensive genomic variations in HERV elements and multiple cancers is still elusive. The purpose of this study is to identify HERV elements with over-representation of somatic mutations and to do the pan-cancer analysis. In the protein coding region, we found four non-canonical HERV elements with over-represented nsSNVs within four genes: TNN (HERV-9), KIR2DL1 (MST), OR4K15 (HERV-IP), and ZNF99 (HERV-W). nsSNVs within class I (HERV-9, HERV-IP and HERV-W) and class III (MST) HERV elements were associated with at least 14 cancer types - notably skin cancer and lung cancer. Based on the differential expression of these four genes in normal and tumor tissue 13 key nsSNVs were found across five cancer types. We showed that kidney cancer patients with the specific mutation C2270G in ZNF99 had a lower survival rate based on a survival analysis. In the non-coding region, we found 788 HERV (both canonical and non-canonical) elements with elevated SNV counts. All SNVs in these 788 HERV elements were located on top of three DNA functional elements: lncRNA (60%), intron (22.2%) and transcriptional factor binding sites (TFBS) (14.8%), in addition to the HERV elements themselves. HERVs overlapping with lncRNA, intron, and TFBS were shown to be associated with skin cancer, esophageal cancer, and liver cancer. This study provides a large-scale analysis investigating the relationship between HERV-involved DNA functional elements and cancers.

Author

• Chang, Ting-Chia

Language

• English

Date created

• 2017

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Biochemistry & Systems Biology

Degree

• M.S.

Advisor

• Mazumder, Raja

Committee Member(s)

• Kumar, Ajit

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/d217qq43c