Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer.
Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer.
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DOI：
10.1016/j.xcrm.2023.100974
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发表时间：
2023-03-21
影响因子：
14.3
通讯作者：
Wang, Meilin
中科院分区：
文献类型：
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作者：
Du, Mulong;Gu, Dongying;Xin, Junyi;Peters, Ulrike;Song, Mingyang;Cai, Guoshuai;Li, Shuwei;Ben, Shuai;Meng, Yixuan;Chu, Haiyan;Chen, Lianmin;Wang, Qianghu;Zhu, Lingjun;Fu, Zan;Zhang, Zhengdon;Wang, Meilin
早发性结直肠癌（EOCRC）的发病率（定义为50岁以下的诊断年龄）正在增加，但其与一般CRC不同的异质性病因仍未确定。我们首先描述了中国CRC队列中79例患者肿瘤的基因组、表观基因组、转录组和蛋白质组。另外126例EOCRC受试者的数据来自国际癌症基因组联盟中国队列和癌症基因组图谱欧洲队列。我们观察到早发性肿瘤具有高肿瘤突变负荷;通过突变特征3和多层途径富集增加DNA修复特征; DNA甲基化和体细胞拷贝数改变对基因表达的影响的强烈扰动;以及作为免疫表型基础的热肿瘤的上调免疫浸润。值得注意的是，LMTK 3表现出祖先突变差异，可能是一种功能性调节剂和生物标志物，驱动EOCRC发展和免疫治疗中的分子改变。这项综合组学研究为CRC的精确肿瘤学提供了有价值的知识。中国人群早发性结直肠癌的综合组学研究组学架构支持早发性肿瘤发生和治疗开发突变景观因血统而异，LMTK 3突变具有中国特异性LMTK 3作用于DNA修复过程、免疫表型和药物靶点早发性结直肠癌的分子特征尚未确定。我们报告了一个中国队列中年轻结直肠肿瘤的多组学景观。这些特征揭示了早发性肿瘤发生中不同的分子改变和免疫表型，并提供了祖先特异性LMTK 3作为精确肿瘤学的调节剂、生物标志物和治疗靶点。
Incidence of early-onset colorectal cancer (EOCRC), defined by a diagnosed age under 50 years, is increasing, but its heterogeneous etiologies that differ from general CRC remain undetermined. We initially characterize the genome, epigenome, transcriptome, and proteome of tumors from 79 patients in a Chinese CRC cohort. Data for an additional 126 EOCRC subjects are obtained from the International Cancer Genome Consortium Chinese cohort and The Cancer Genome Atlas European cohort. We observe that early-onset tumors have a high tumor mutation burden; increased DNA repair features by mutational signature 3 and multi-layer pathway enrichments; strong perturbations at effects of DNA methylation and somatic copy-number alteration on gene expression; and upregulated immune infiltration as hot tumors underlying immunophenotypes. Notably, LMTK3 exhibits ancestral mutation disparity, potentially being a functional modulator and biomarker that drives molecular alterations in EOCRC development and immunotherapies. This integrative omics study provides valuable knowledge for precision oncology of CRC. An integrative omics study of early-onset colorectal cancer in a Chinese cohort Omics architecture supports early-onset tumorigenesis and therapeutic development Mutational landscape varies by ancestry, and LMTK3 mutation has Chinese specificity LMTK3 works at DNA repair process, immunophenotype, and drug target The molecular characterization of early-onset colorectal cancer remains undetermined. We report a multi-omics landscape of young colorectal tumors in a Chinese cohort. These profiles reveal distinct molecular alterations and immunophenotypes in early-onset tumorigenesis and provide an ancestry-specific LMTK3 as a modulator, biomarker, and therapeutic target for precision oncology.
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DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP
影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
影响因子：
28.2
作者：
通讯作者：
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使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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