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A multilevel pan-cancer map links gene mutations to cancer hallmarks

Chinese Journal of Cancer 2015年第10期34卷 439-449页

作者： Theo A.Knijnenburg Tycho Bismeijer Lodewyk F.A.Wessels llya Shmulevich Institute for Systems Biology Bioinformatics and Statistics Division of Molecular CarcinogenesisNetherlands Cancer Institute

Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are *** study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics ***:We created a map that connects genes to cancer hallmarks via signaling *** projected gene mutation and focal copy number data from various cancer types onto this *** performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this ***:Our analysis showed that although the genetic fingerprint of tumor types could be very different,there were less variations at the level of hallmarks,consistent with the idea that different genetic alterations have similar functional ***,we showed how the multilevel map could help to clarify the role of infrequently mutated genes,and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways,whereas many co-occurring gene mutations were associated with hallmark ***:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks.

关键词： Cancer systems biology, Cancer hallmarks, Gene mutations, Multilevel model

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