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Principal Investigator: Eric Banks
Organization: BROAD INSTITUTE, INC.
Fiscal Year: 2021
Award: $78,000
Funding agency: National Cancer Institute
Abstract/Summary
Viruses play a role in 10 to 20% of human cancers. Tying specific viruses to human cancers remains a
fundamental biomedical and technological problem. One virus family, the human papillomaviruses (HPVs),
comprises over 225 known types and causes lesions ranging from benign warts to highly lethal, invasive
carcinomas. HPV-induced tumors occur at several anatomical sites including nearly 100% of cervical
cancers, 90% of anal cancers, 30 to 60% of head & neck tumors, and roughly one-fourth to one-half of vaginal,
vulvar & penile cancers. In most HPV-induced tumors, at least part of the viral DNA genome has become
integrated into the human genome, presumably as a consequence of aberrant host cell DNA repair processes.
Our laboratory work has been focused on the development of accurate, sensitive, broad specificity technology
based on DNA hybridization capture plus massively parallel sequencing to detect and structurally analyze
integrated HPV DNA in precancerous lesions and invasive tumors. Ongoing studies are also developing
fluorescent microscopy technologies for detection of both integrated HPV DNA and HPV RNA transcripts, as
these provide highly specific, potential diagnostic tools to detect the presence of HPV-induced tumor cells,
including post-therapy residual disease in clinical samples. Our work encompasses long-range, nanopore
DNA sequencing plus RNA sequencing to confirm any complex structural rearrangements of the HPV and
human genomes and to elucidate potential viral effects on viral and human gene transcription. Key to these
studies has been a very successful, collaborative effort by the Haas group (Broad Institute at MIT) with the
Lenz (Albert Einstein College of Medicine) and Montagna (Rutgers Cancer Institute of New Jersey) labs to
expand the computational tools of the Trinity Cancer Transcriptome Analysis Toolkit (CTAT). This has led to
the development of expanded CTAT components for detection of integrated HPV DNA, structural assembly
of integrated viral DNA segments, and overall transcriptional analysis of HPV-induced tumors and
precancerous lesions. The CTAT-virus insertion finder (CTAT-VIF) is available on GitHub. The IMAT-ITCR
collaboration proposed here will substantially expand the ongoing collaboration by pursuing three additional
aims. Aim 1 will expand CTAT-VIF to analyze the presence of ~13,000 different viruses and investigate if
any viral DNAs are integrated and/or expressed by screening all The Cancer Genome Atlas (TCGA) and
Genotype-Tissue Expression Project (GTEx) datasets. Aim 2 is to identify and analyze novel virus-human
fusion transcripts generated from virus DNA insertions. Aim 3 will broaden our in-situ analysis of HPV-
induced cervical cancers and precancerous lesions to include spatial transcriptomic analysis, including
expanding CTAT for this technology. These studies should improve computational and laboratory
technologies for understanding the roles of viruses in human cancer.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Administrative Supplement><Affect><Anal Cancer><Anal Cancers><Anatomic><Anatomic Sites><Anatomic structures><Anatomical Sciences><Anatomy><Aneuploid><Aneuploidy><Anus Cancer><Benign><Body Tissues><CINJ><COVID-19 virus><COVID19 virus><Cancer Institute of New Jersey><Cancers><Carcinoma><Cell Body><Cells><Cervical><Cervical Cancer><Cervix Cancer><Clinical><Cloud Computing><Cloud Infrastructure><CoV-2><CoV2><Collaborations><Complex><Computational Biology><Computer software><DNA><DNA Damage Repair><DNA Integration><DNA Repair><DNA Structure><DNA Viruses><DNA seq><DNA sequencing><DNAseq><Data><Data Set><Dataset><Deoxyribonucleic Acid><Detection><Development><Diagnostic><Epithelial cancer><FISH Technic><FISH Technique><FISH analysis><FISH assay><Family><Fluorescence In Situ Hybridization><Fluorescent in Situ Hybridization><Foundations><GTEx><Gene Amplification><Gene Expression><Gene Transcription><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Genome><Genomics><Genotype-Tissue Expression Project><Goals><HCV><HPV><Head and Neck Neoplasms><Hepatitis B><Hepatitis B Infection><Hepatitis C virus><High-Throughput Nucleotide Sequencing><High-Throughput Sequencing><Histologic><Histologically><Human><Human Genome><Human Papilloma Virus><Human Papillomavirus><In Situ><Infectious Human Wart Virus><Institutes><Laboratories><Length><Lesion><Malignant Anal Neoplasm><Malignant Anal Tumor><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Epithelial Neoplasms><Malignant Epithelial Tumors><Malignant Neoplasm of the Cervix><Malignant Neoplasms><Malignant Penile Neoplasm><Malignant Penile Tumor><Malignant Tumor><Malignant Tumor of the Anus><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Tumor of the Penis><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant Vagina Neoplasm><Malignant Vagina Tumor><Malignant Vaginal Neoplasm><Malignant Vaginal Tumor><Malignant Vulva Tumor><Malignant Vulvar Neoplasm><Malignant Vulvar Tumor><Malignant neoplasm of anus><Malignant neoplasm of cervix uteri><Malignant neoplasm of penis><Malignant neoplasm of vulva><Massive Parallel Sequencing><Massively Parallel DNA Sequencing><Massively Parallel Sequencing><Medicine><Messenger RNA><Methods><Microscopy><Modern Man><Molecular><Molecular Computations><Mutation><Non-Polyadenylated RNA><Oncogenesis><Oncogenic Viruses><Pattern><Penile Cancer><Penis Cancer><Play><Process><Proteins><Publishing><RNA><RNA Expression><RNA Gene Products><RNA Seq><RNA Viruses><RNA sequencing><RNAseq><Reporting><Residual Tumors><Resolution><Ribonucleic Acid><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Scientist><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Site><Software><Somatic Mutation><Specificity><Structure><TCGA><Technology><The Cancer Genome Atlas><Tissues><Transcript><Transcription><Tumor Cell><Tumor Viruses><Unscheduled DNA Synthesis><Uterine Cervix Cancer><Vagina Cancer><Vaginal Cancers><Viral><Viral Diseases><Viral Genome><Viral Hepatitis B><Virus><Virus Diseases><Virus Integration><Vulva Cancer><Vulvar Cancer><Work><Wuhan coronavirus><anal squamous cell carcinoma><base><cancer genomics><cancer initiation><cancer progression><cloud computer><college><collegiate><computational tools><computer biology><computerized tools><coronavirus disease 2019 virus><developmental><epithelial carcinoma><gamma-herpesvirus><gammaherpesvirus><genome mutation><global gene expression><global transcription profile><hCoV19><head and neck tumor><histopathologic examination><histopathological examination><human DNA><human whole genome><improved><infection with HBV><infection with hepatitis B virus><insight><lab equipment><laboratory equipment><laboratory technology><mRNA><malignancy><nCoV2><nano pore><nanopore><natural gene amplification><neo-antigen><neo-epitopes><neoantigens><neoepitopes><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><novel><novel virus><oncogenomics><precancerous><premalignant><reference assembly><reference genome><residual disease><screening><serum hepatitis><social role><tool><transcriptome><transcriptome sequencing><transcriptomics><tumor><tumor progression><tumorigenesis><viral DNA><viral infection><viral integration><virology><virus DNA><virus genome><virus infection><virus-induced disease><vulval cancer><wart virus><γ-herpesvirus>