Department of Clinical Immunology, Institute of Clinical Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China.
Department of Laboratory Medicine and.
Am J Med Sci. 2019 Nov;358(5):340-349. doi: 10.1016/j.amjms.2019.07.012. Epub 2019 Aug 1.
This study analyzed multiple parameters including somatic single nucleotide variations (SNVs), Insertion/Deletions, significantly mutated genes (SMGs), copy number variations and frequently altered pathways aims to discover novel aberrances in the tumorigenesis of colorectal cancer (CRC).
Exome sequencing was performed on an Illumina platform to identify novel potential somatic variances in 34 paired tumor and adjacent normal tissues from 17 CRC patients. Results were compared with databases (dbSNP138, 1000 genomes SNP, Hapmap, Catalogue of Somatic Mutation of Cancer and ESP6500) and analyzed. MuSic software was used to identify SMGs.
In total, 1,637 somatic SNVs in 17 analyzed tumors were identified. Only 7 SNVs were shared by more than 1 tumor, suggesting that over 99% of the analyzed SNVs were independent events. Mutation of KRAS p. G12D and ZNF717 p. L39V were the most common SNVs. Moreover, 10 SMGs namely KRAS, TP53, SMAD4, ZNF717, FBXW7, APC, ZNF493, CDR1, the Armadillo repeat containing 4 (ARMC4) and sulfate-modifying factor 2 (SUMF2) were found. Among those, ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 were novel frequent genes in CRC. For copy number variations analysis, gains in 10q25.3, 1p31.1, 1q44, 10q23.33, 11p15.4 and 20q13.33, and loss of 3q21.3 and 3q29 were frequent aberrations identified in our results.
We frequently found novel genes ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 and gains in 10q25.3, which may be functional mutation in CRC. The high-frequency private events such as SNVs confirm the highly heterogeneous mutations found in CRCs. The mutated genes sites in different patients may vary significantly, which may also be more challenging for clinical treatment.
本研究分析了多种参数，包括体细胞单核苷酸变异（SNV）、插入/缺失、显著突变基因（SMG）、拷贝数变异和频繁改变的途径，旨在发现结直肠癌（CRC）发生过程中的新的异常。
对 17 例 CRC 患者的 34 对肿瘤和癌旁正常组织进行了 Illumina 平台的外显子组测序，以鉴定新的潜在体细胞变异。将结果与数据库（dbSNP138、1000 基因组 SNP、Hapmap、癌症体细胞突变目录和 ESP6500）进行比较和分析。使用 MuSic 软件识别 SMG。
在分析的 17 个肿瘤中共鉴定出 1637 个体细胞 SNV。只有 7 个 SNV 被超过 1 个肿瘤共享，这表明超过 99%的分析 SNV 是独立事件。KRAS p.G12D 和 ZNF717 p.L39V 的突变是最常见的 SNV。此外，还发现了 10 个 SMG，即 KRAS、TP53、SMAD4、ZNF717、FBXW7、APC、ZNF493、CDR1、富含 Armadillo 重复的 4（ARMC4）和硫酸盐修饰因子 2（SUMF2）。其中，ZNF717、ZNF493、CDR1、ARMC4 和 SUMF2 是 CRC 中的新的高频基因。在拷贝数变异分析中，我们发现 10q25.3、1p31.1、1q44、10q23.33、11p15.4 和 20q13.33 的获得以及 3q21.3 和 3q29 的缺失是我们研究中常见的异常。
我们经常发现新的基因 ZNF717、ZNF493、CDR1、ARMC4 和 SUMF2 以及 10q25.3 的获得，这可能是 CRC 中的功能突变。高频的私有事件，如 SNV，证实了 CRC 中存在高度异质性的突变。不同患者的突变基因位点可能有显著差异，这也可能对临床治疗更具挑战性。
