Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

A genetic model for colorectal tumorigenesis

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.

Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal

Methods of assessing tumor growth

PD3-3-4: Vandetanib in advanced NSCLC: an ongoing clinical evaluation program

Source Citation Chlebowski RT, Schwartz AG, Wakelee H, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised...

Estrogen plus progestin increased lung cancer mortality but not incidence in postmenopausal women

e19030 Background: Interstitial lung diseases are associated with increased risk of lung cancer. A radiographic scoring method of interstitial lung abnormalities (ILA) on CT was previously reported...

Interstitial lung abnormalities in treatment-naive advanced NSCLC patients (pts): Prevalence and impact on survival.

Asymmetric dimerization of the kinase domain is a key mechanism for activation of the epidermal growth factor receptor (EGFR). Here, we show that whereas wild‐type EGFR and the L858R mutant require dimerization for activation and oncogenic transformation, the exon 19 deletion, exon 20 insertion, and L858R/T790M EGFR mutants do not require dimerization. Consistent with these findings, tyrosine phosphorylation of the carboxyl‐terminus is not required for mutant EGFR‐mediated cellular transformation. These differences in dimerization requirements may have clinical implications: treatment with the monoclonal antibody, cetuximab, shrinks mouse lung tumors induced by the dimerization‐dependent L858R mutant, but exerts only a modest effect on tumors driven by dimerization‐independent EGFR mutants. These data imply that disruption of dimerization is among the antitumor mechanisms of cetuximab. We therefore hypothesize that EGFR mutation status in lung cancers may serve as a marker for clinical response to cetuximab. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A177.

Bruce E. Johnson

Papers

Methods of assessing tumor growth

PD3-3-4: Vandetanib in advanced NSCLC: an ongoing clinical evaluation program

Estrogen plus progestin increased lung cancer mortality but not incidence in postmenopausal women

Interstitial lung abnormalities in treatment-naive advanced NSCLC patients (pts): Prevalence and impact on survival.

Abstract A177: Cetuximab resistance associated with dimerization‐independence of oncogenic EGFR mutants