CellNetworks, Bioquant, Im Neuenheimer Feld 267, University of Heidelberg, 69120 Heidelberg, Germany.
Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, University of Heidelberg, 69120 Heidelberg, Germany.
Sci Rep. 2016 Oct 4;6:34490. doi: 10.1038/srep34490.
To attain a deeper understanding of diseases like cancer, it is critical to couple genetics with biomolecular mechanisms. High-throughput sequencing has identified thousands of somatic mutations across dozens of cancers, and there is a pressing need to identify the few that are pathologically relevant. Here we use protein structure and interaction data to interrogate nonsynonymous somatic cancer mutations, identifying a set of 213 molecular interfaces (protein-protein, -small molecule or -nucleic acid) most often perturbed in cancer, highlighting several potentially novel cancer genes. Over half of these interfaces involve protein-small-molecule interactions highlighting their overall importance in cancer. We found distinct differences in the predominance of perturbed interfaces between cancers and histological subtypes and presence or absence of certain interfaces appears to correlate with cancer severity.
为了更深入地了解癌症等疾病，将遗传学与生物分子机制相结合至关重要。高通量测序已经在数十种癌症中鉴定出数千个体细胞突变，现在迫切需要确定少数与病理相关的突变。在这里，我们使用蛋白质结构和相互作用数据来研究非同义体细胞癌症突变，确定了一组在癌症中经常受到干扰的 213 个分子界面（蛋白质-蛋白质、-小分子或 -核酸），突出了几个潜在的新型癌症基因。这些界面中有一半以上涉及蛋白质-小分子相互作用，突出了它们在癌症中的总体重要性。我们发现，在癌症和组织学亚型之间，受干扰界面的优势存在明显差异，某些界面的存在或缺失似乎与癌症的严重程度相关。
