Characterizing Heterogeneity In Kras Mutant Colorectal Cancers (Crc) Using Cellular, Mutation, And Immune Profiles.

JOURNAL OF CLINICAL ONCOLOGY(2018)

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摘要
657Background: Approximately 30%-50% of CRC patients have KRAS mutation, and they are associated with lack of treatment response to anti-EGFR therapy. KRAS mutant CRCs are heterogeneous that not all mutant tumors are dependent on its downstream signaling. At this era of the search for therapeutic targets related to mutant KRAS, it is essential to understand the underlying heterogeneity in KRAS mutant metastatic CRCs with a goal of identifying personalized therapeutic vulnerabilities. To understand KRAS mutation further, in this study we classified KRAS mutant CRCs based on individual cell types in the normal colon crypt and associated them with PIK3CA mutations and interferon-gamma responsive signature. Methods: Publicly available RNAseq gene expression data from KRAS mutant samples were used. Classification of CRC samples into CRCassigner subtypes, KRAS mutation dependents/independent groups, and interferon gamma-responsive status was performed using published signatures. Results: CRC samples (nu003e200) wit...
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