Clinical-grade whole-genome sequencing and 3′ transcriptome analysis of colorectal cancer patients

Autor: Miao He, Mark T. Ross, Agata Stodolna, Daniel Blakeway, Mahesh Vasipalli, Joanne D. Stockton, Stephen T. Ward, Andrew D Beggs, Tariq Ismail, Jennifer Becq, Toju Sillo, Mark P Dilworth, Zoya Kingsbury, Jonathan James
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Colorectal cancer
lcsh:Medicine
Disease
Genome
Transcriptome
0302 clinical medicine
Databases
Genetic
Medicine
Cluster Analysis
RNA-Seq
Rectal cancer
Genetics (clinical)
Aged
80 and over
0303 health sciences
Chemoradiotherapy
Genomics
Middle Aged
Telomere
3. Good health
Gene Expression Regulation
Neoplastic
Phenotype
030220 oncology & carcinogenesis
Molecular Medicine
Female
Colorectal Neoplasms
Adult
lcsh:QH426-470
DNA Copy Number Variations
Antineoplastic Agents
Computational biology
03 medical and health sciences
Genetics
Humans
Molecular Biology
Gene
Germ-Line Mutation
030304 developmental biology
Aged
Whole genome sequencing
Pathological complete response
Whole Genome Sequencing
business.industry
Research
Gene Expression Profiling
lcsh:R
Oncogenes
medicine.disease
Human genetics
lcsh:Genetics
Mutation
business
Zdroj: Genome Medicine
Genome Medicine, Vol 13, Iss 1, Pp 1-15 (2021)
ISSN: 1756-994X
Popis: Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of > 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.
Databáze: OpenAIRE
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