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

Genome Medicine

Mahesh Vasipalli¹  Mark T. Ross¹  Miao He¹  Zoya Kingsbury¹  Jennifer Becq¹  Jonathan James²  Daniel Blakeway²  Agata Stodolna²  Mark P. Dilworth²  Toju Sillo²  Joanne D. Stockton²  Andrew D. Beggs³  Stephen T. Ward⁴  Tariq Ismail⁴ 

[1] Illumina Cambridge, Granta Park, Cambridge, UK;Institute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;Institute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;Surgical Research Laboratory, Institute of Cancer & Genomic Science, University of Birmingham, Vincent Drive, B15 2TT, Birmingham, UK;University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK;

关键词: Pathological complete response;    Chemoradiotherapy;    Rectal cancer;    Genomics;   

DOI  :  10.1186/s13073-021-00852-8

来源: Springer

【 摘 要 】

BackgroundClinical-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.MethodsPatients 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.ResultsFifty-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.ConclusionsClinical 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.

【 授权许可】

CC BY