Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients
Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients
Abstract IntroductionClinical grade whole genome sequencing (cWGS) has the potential to become 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 mutational signatures and tumour biology were gained by the use of 3’ RNAseq. 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 20% 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 identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.
Stodolna Agata、Sillo Toju、Ward Stephen T、Ismail Tariq、Ross Mark T.、Vasipalli Mahesh、Kingsbury Zoya、Becq Jennifer、Dilworth Mark P、He Miao、James Jonathan、Blakeway Daniel、Beggs Andrew D.、Stockton Joanne D
Institute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamUniversity Hospitals Birmingham NHS Foundation TrustUniversity Hospitals Birmingham NHS Foundation TrustIllumina CambridgeIllumina CambridgeIllumina CambridgeIllumina CambridgeInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamIllumina CambridgeInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of BirminghamInstitute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of Birmingham
医学研究方法肿瘤学基础医学
Pathological complete responseChemoradiotherapyRectal cancerGenomics
Stodolna Agata,Sillo Toju,Ward Stephen T,Ismail Tariq,Ross Mark T.,Vasipalli Mahesh,Kingsbury Zoya,Becq Jennifer,Dilworth Mark P,He Miao,James Jonathan,Blakeway Daniel,Beggs Andrew D.,Stockton Joanne D.Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients[EB/OL].(2025-03-28)[2025-05-02].https://www.medrxiv.org/content/10.1101/2020.04.26.20080887.点此复制
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