Clinical-grade whole-genome sequencing and 3' transcriptome analysis of colorectal cancer patients.
Clinical-grade whole-genome sequencing and 3' transcriptome analysis of colorectal cancer patients.
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DOI：
10.1186/s13073-021-00852-8
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发表时间：
2021-02-25
期刊：
影响因子：
12.3
通讯作者：
Beggs AD
中科院分区：
文献类型：
--
作者：
Stodolna A;He M;Vasipalli M;Kingsbury Z;Becq J;Stockton JD;Dilworth MP;James J;Sillo T;Blakeway D;Ward ST;Ismail T;Ross MT;Beggs AD
临床级全基因组测序（cWGS）有潜力成为临床护理的标准，因为它覆盖范围广，对基因组的某些区域没有偏见。结直肠癌是一种困难的治疗模式，超过40%的患者在诊断时出现转移性疾病。我们假设cWGS结合3 '转录组分析将为结直肠癌提供新的见解。患者进行了无pcr全基因组测序和比对，并使用标准化管道进行变异调用，以输出snv、indel、sv和CNAs。通过使用3 ' RNA-seq获得了对突变特征和肿瘤生物学的更多见解。共研究了54例患者。驱动因素分析确定Wnt通路基因APC是结直肠癌中唯一持续突变的驱动因素。PI3K/mTOR通路的改变与之前在结直肠癌中观察到的一样。多个私有CNAs、SVs和基因融合对于单个肿瘤是独特的。大约30%的患者的肿瘤突变负荷为bb10突变/Mb DNA，表明适合免疫治疗。临床全基因组测序为鉴定个体基因组变异提供了一条潜在途径，这可能赋予患者对靶向药物的敏感性，并为患者提供靶向治疗的新选择。在线版本包含补充材料，可在10.1186/s13073-021-00852-8获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s13073-021-00852-8.
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影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
端粒：一种倍性 - 敏锐的方法，用于从整个基因组测序数据中估算端粒长度。
影响因子：
4.6
作者：
Farmery JHR;Smith ML;NIHR BioResource - Rare Diseases;Lynch AG
通讯作者：
Lynch AG
影响因子：
16.6
作者：
Ishaque N;Abba ML;Hauser C;Patil N;Paramasivam N;Huebschmann D;Leupold JH;Balasubramanian GP;Kleinheinz K;Toprak UH;Hutter B;Benner A;Shavinskaya A;Zhou C;Gu Z;Kerssemakers J;Marx A;Moniuszko M;Kozlowski M;Reszec J;Niklinski J;Eils J;Schlesner M;Eils R;Brors B;Allgayer H
通讯作者：
Allgayer H
影响因子：
5
作者：
Druliner BR;Rashtak S;Ruan X;Bae T;Vasmatzis N;O'Brien D;Johnson R;Felmlee-Devine D;Washechek-Aletto J;Basu N;Liu H;Smyrk T;Abyzov A;Boardman LA
通讯作者：
Boardman LA
影响因子：
48
作者：
Gonzalez-Perez A;Perez-Llamas C;Deu-Pons J;Tamborero D;Schroeder MP;Jene-Sanz A;Santos A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N