Sutton P A, Jithesh P V, Jones R P, Evans J P, Vimalachandran D, Malik H Z, Park B K, Goldring C E, Palmer D H, Kitteringham N R
Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GE, UK.
Sidra Medical and Research Centre, Doha, Qatar.
Eur J Surg Oncol. 2018 Jan;44(1):115-121. doi: 10.1016/j.ejso.2017.10.211. Epub 2017 Nov 13.
Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour.
We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis.
Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226 (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours.
Only 13.8% of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.
新一代测序技术推动了结直肠癌基因型的图谱绘制，并加深了我们对转移发生的理解。本研究的目的是调查同期切除的原发性结直肠癌和肝转移瘤外显子组中的保守和不同突变。这些信息有可能借助原发性肿瘤的生物学信息来指导晚期疾病的治疗。
我们对4例接受新辅助化疗的患者同期切除的原发性结直肠癌、结直肠癌肝转移瘤以及正常结肠黏膜和肝实质进行了外显子组测序，使用Ion Proton平台，测序深度为50X。在进行变异检测、注释和下游分析之前，将原始数据映射到参考基因组。
外显子组测序鉴定出585个非同义错义单核苷酸变异（SNV），其中215个（36.8%）是原发性肿瘤特有的，226个（38.6%）是转移瘤特有的，81个（13.8%）存在于患者匹配对中。在原发性和转移性肿瘤中，在表皮生长因子受体（ErbB）途径中鉴定出的SNV似乎是一致的。
只有13.8%的转移瘤外显子组可以通过原发性肿瘤的基因型预测。我们已经证明了ErbB途径中一些SNV的一致性，这可能为晚期结直肠癌治疗药物的选择提供依据。
