Discovery of Aberrant Alteration of Genome in Colorectal Cancer by Exome Sequencing
Discovery of Aberrant Alteration of Genome in Colorectal Cancer by Exome Sequencing
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DOI：
10.1016/j.amjms.2019.07.012
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发表时间：
2019-11-01
影响因子：
3.1
通讯作者：
Xu, Jun-Fa
中科院分区：
文献类型：
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作者：
Liang, Yuanzi;Jiang, Liejun;Xu, Jun-Fa
背景：本研究分析了体细胞单核苷酸变异（SNVs）、插入/缺失、显著突变基因（SMGs）、拷贝数变异和常变通路等多个参数，旨在发现结直肠癌（CRC）发生过程中的新异常。材料和方法：在Illumina平台上进行外显子组测序，以鉴定来自17例结直肠癌患者的34对肿瘤和邻近正常组织的新的潜在体细胞变异。结果与数据库（dbSNP138、1000 genomes SNP、Hapmap、Catalogue of Somatic Mutation of Cancer和ESP6500）进行对比分析。使用MuSic软件识别smg。结果：在17个分析的肿瘤中共鉴定出1637个体细胞snv。只有7个snv存在于1个以上的肿瘤中，表明99%以上的snv是独立事件。KRAS p. G12D和ZNF717 p. L39V是最常见的snv。此外，还发现了KRAS、TP53、SMAD4、ZNF717、FBXW7、APC、ZNF493、CDR1、Armadillo repeat containing 4 （ARMC4）和硫酸盐修饰因子2 （SUMF2）等10个SMGs。其中，ZNF717、ZNF493、CDR1、ARMC4和SUMF2是结直肠癌中新的常见基因。对于拷贝数变异分析，10q25.3、1p31.1、1q44、10q23.33、11p15.4和20q13.33的增加以及3q21.3和3q29的缺失是我们结果中发现的常见畸变。结论：我们在10q25.3中频繁发现新的基因ZNF717、ZNF493、CDR1、ARMC4和SUMF2，这些基因可能在CRC中发生功能性突变。高频率的私人事件，如snv，证实了在crc中发现的高度异质突变。不同患者的突变基因位点可能存在显著差异，这也给临床治疗带来了更大的挑战。
Background: 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).Materials and Methods: 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.Results: 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.Conclusions: 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.