patient-oriented gene set analysis for cancer mutation datapatient-oriented癌症突变基因集合分析数据.pdfVIP

Boca et al. Genome Biology 2010, 11:R112 /2010/11/11/R112 METHOD Open Access Patient-oriented gene set analysis for cancer mutation data 1 2 2 2 3* Simina M Boca , Kenneth W Kinzler , Victor E Velculescu , Bert Vogelstein , Giovanni Parmigiani Abstract Recent research has revealed complex heterogeneous genomic landscapes in human cancers. However, mutations tend to occur within a core group of pathways and biological processes that can be grouped into gene sets. To better understand the significance of these pathways, we have developed an approach that initially scores each gene set at the patient rather than the gene level. In mutation analysis, these patient-oriented methods are more transparent, interpretable, and statistically powerful than traditional gene-oriented methods. Background processes may provide more information about the path- To date, the sequences of all coding exons (the exome) ways altered in cancers than an analysis of individual have been determined in 74 cancers [1-8]. These studies genes. have revealed that advanced cancers each generally Sequencing studies completed prior to those involving harbor between 30 and 80 point mutations or small large scale sequencing have additionally revealed an insertions or deletions. Other genetic alterations, such as ‘exclusivity principle’. Within a single pathway, it is rare amplifications and homozygous deletions, contribute for multiple genes to be altered in a single tumor. Thus a another ten genes per tumor. These alterations can be tumor with a KRAS mutation g