BGI-Shenzhen, Shenzhen 518083, China.
BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
Biomed Res Int. 2020 Jul 17;2020:2861240. doi: 10.1155/2020/2861240. eCollection 2020.
This study was aimed at investigating the mutations in colorectal cancer (CRC) for recurrent neoantigen identification. A total of 1779 samples with whole exome sequencing (WES) data were obtained from 7 published CRC cohorts. Common HLA genotypes were used to predict the probability of neoantigens at high-frequency mutants in the dataset. Based on the WES data, we not only obtained the most comprehensive CRC mutation landscape so far but also found 1550 mutations which could be identified in at least 5 patients, including G12D (8%), G12V (5.8%), E545K (3.5%), H1047R (2.5%), and N583Tfs∗44 (2.8%). These mutations can also be recognized by multiple common HLA molecules in Chinese and TCGA cohort as potential "public" neoantigens. Many of these mutations also have high mutation rates in metastatic pan-cancers, suggesting their value as therapeutic targets in different cancer types. Overall, our analysis provides recurrent neoantigens as potential cancer immunotherapy targets.
本研究旨在通过分析结直肠癌（CRC）的突变情况来识别复发性新生抗原。本研究共纳入了 7 个已发表的 CRC 队列中的 1779 个全外显子组测序（WES）样本。利用常见的 HLA 基因型来预测数据集高频突变中新抗原的出现概率。基于 WES 数据，我们不仅获得了迄今为止最全面的 CRC 突变图谱，还发现了 1550 个至少能在 5 个患者中识别的突变，包括 G12D（8%）、G12V（5.8%）、E545K（3.5%）、H1047R（2.5%）和 N583Tfs∗44（2.8%）。这些突变也可以被中国和 TCGA 队列中的多个常见 HLA 分子识别为潜在的“公共”新生抗原。这些突变中有许多在转移性泛癌中也具有较高的突变率，提示它们在不同癌症类型中作为治疗靶点的价值。总之，我们的分析为癌症免疫治疗提供了复发性新生抗原作为潜在的治疗靶点。
