RT Dissertation/Thesis
T1 The genomic landscape of somatic viral integration in cancer
A1 García Álvarez, Eva
K1 cancer genomics
K1 viral integrations
K1 NGS
K1 TGS
AB Viruses cause 10-15% of human cancers worldwide and some oncogenicviruses nucleic acid may become integrated into the human genome. This process can induce tumours, amechanism called insertional mutagenesis. The present work aims to shed light on viral integrations in cancer,detecting and characterising somatic Hepatitis B virus (HBV) integrations in hepatocellular carcinoma (HCC)samples from the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. In addition, a new tool for thedetection of viral integrations in both, Next Generation and Third Generation Sequencing data, is presented here.This pipeline was used for the analysis of human cancer samples HBV and Human Papillomavirus (HPV) positiveand cell lines Kaposis Sarcoma Herpesvirus (KSHV) positive. These analyses revealed that non-canonical HBVinsertions occur in association with megabase-size deletions that remove telomeric regions of chromosomes andcan cause the loss of tumour suppressor genes. Furthermore, we found that HBV somatic insertions in HCC aretypically acquired early in tumour evolution. In addition, VIRUNS (VIral-Reference UNions Search) was developed.It was benchmarked using in silico genomes and compared with three short-read integration detection tools,displaying the best balance between precision and recall. VIRUNS successfully characterised HPV integrations inthe PCAWG dataset, which are usually coupled with local sequencing coverage changes. Finally, KSHV-humanDNA junctions, not described until the moment, were detected by VIRUNS in two primary effusion lymphoma celllines.
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29338
UL http://hdl.handle.net/10347/29338
LA eng
DS Minerva
RD 26 abr 2026