The consensus molecular subtypes of colorectal cancer.
The consensus molecular subtypes of colorectal cancer.
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DOI：
10.1038/nm.3967
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发表时间：
2015-11
期刊：
影响因子：
82.9
通讯作者：
Tejpar S
中科院分区：
文献类型：
--
作者：
Guinney J;Dienstmann R;Wang X;de Reyniès A;Schlicker A;Soneson C;Marisa L;Roepman P;Nyamundanda G;Angelino P;Bot BM;Morris JS;Simon IM;Gerster S;Fessler E;De Sousa E Melo F;Missiaglia E;Ramay H;Barras D;Homicsko K;Maru D;Manyam GC;Broom B;Boige V;Perez-Villamil B;Laderas T;Salazar R;Gray JW;Hanahan D;Tabernero J;Bernards R;Friend SH;Laurent-Puig P;Medema JP;Sadanandam A;Wessels L;Delorenzi M;Kopetz S;Vermeulen L;Tejpar S
结直肠癌（CRC）是一种常见的致死性疾病，具有异质性结局和药物反应。为了解决报告的基于基因表达的CRC分类之间的不一致性并促进临床翻译，我们成立了一个国际联盟，致力于跨专家组的大规模数据共享和分析。我们显示了六个独立的分类系统之间的显着互连性，这些系统合并成四个具有显着特征的共识分子亚型（CMS）：CMS 1（MSI免疫，14%），高度突变，微卫星不稳定，强免疫激活; CMS 2（典型，37%），上皮，染色体不稳定，显著WNT和MYC信号传导激活; CMS 3（代谢，13%），上皮，明显的代谢失调;和CMS 4（间充质，23%），显著的转化生长因子β激活，基质侵袭和血管生成。具有混合特征的样本（13%）可能代表过渡表型或肿瘤内异质性。我们认为CMS组是目前可用于CRC的最稳健的分类系统-具有明确的生物学可解释性-并且是未来临床分层和基于亚型的靶向干预的基础。
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions.