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

Stodolna, Agata, He, Miao, Vasipalli, Mahesh, Kingsbury, Zoya, Becq, Jennifer, Stockton, Joanne D, Dilworth, Mark P, James, Jonathan, Sillo, Toju, Blakeway, Daniel, Ward, Stephen T, Ismail, Tariq, Ross, Mark T and Beggs, Andrew D (2021) Clinical-grade whole-genome sequencing and 3' transcriptome analysis of colorectal cancer patients. Genome medicine, 13 (1). p. 33. ISSN 1756-994X. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Abstract

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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
WO Surgery
Divisions: Planned IP Care > Oncology and Clinical Haematology
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 10 Mar 2021 15:08
Last Modified: 10 Mar 2021 15:08
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4068

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