Thesis (Ph.D)

Insertionally polymorphic human endogenous retroviruses and their potential role in cancer


In this study a family of endogenous retroviruses, HERV-K(HML-2) was investigated. The family is the youngest endogenous retrovirus family known in humans, with some of its members being insertionally polymorphic in modern human populations. There have been numerous reports of HERV-K(HML-2) members being present in cancer samples. Here, a robust analysis of the state of HERV-K(HML-2) family in the human genome known to date is presented, along with the most complete database of known insertions, present in modern human genomes. In addition to literature data, 10 novel solo-LTR elements and 2 novel full-length truncated elements, found in recent assemblies of the Human reference genome are reported in this study. Furthermore, a bioinformatics pipeline used to detect HERV-K(HML-2) loci in genomic sequence data is presented. The pipeline is used to analyze a large dataset of 11 different cancer sequencing projects coming from The Cancer Genome Atlas, resulting in detection of 28 polymorphic insertions. 7 of these are thought to be completely novel, whereas 10 display significance in occurrence rate when comparing the cancer data to general population. A number of biochemical pathways suspected to be altered by the detected insertions were found. Nevertheless, the low frequency of occurrence for novel HERV-K(HML2) insertions detected in this study, combined with absence of novel insertions detected in cancer tissue only suggest, that the hypothesis of HERV-K(HML-2) elements being still active in modern human populations is unlikely. However, significant presence of unfixed insertions in cancer samples combined with a list of genes known to be altered in cancer and influenced by these loci suggest, that presence of these particular loci could influence cancer development and progression.

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Izydorczyk, Michal


Supervisors: Kanda, Ravinder K; Brooks, Susan

Oxford Brookes departments

Faculty of Health and Life Sciences
Department of Biological and Medical Sciences


Year: 2022

© Izydorczyk, Michal
Published by Oxford Brookes University
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  • Owner: Michal Izydorczyk
  • Collection: eTheses
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