2016ASCOMET通路进展研究讲述.ppt

* BID, twice daily; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; QD, once daily; RP2D, recommended Phase II dose. * * * * * * * * * * * 美国加利福尼亚大学医学院Sai-Hong Ignatius Ou教授 MET exon 14 skipping (METex14) has recently been described a potential driver alteration in lung cancer targetable by MET tyrosine kinase inhibitors (TKIs) (PMID:. However, a large series of lung cancer cases harboring METex14 alterations has not been reported hybridizationg capture of at least 3769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer samples were prospectively sequenced to high(average 820X) uniform coverage as part of routine clinical practice(August 2012-November 2015) patient samples were evaluated for genomic alterations(GAs) including base pair substitutions, insertions/deletions, copy number alterations and rearrangements. These GAs were then manually inspected to identify those likely to affect splicing of MET exon 14, or to delete the exon entirely Ordinal relationships were examined using the Mann-Whitney U-Test; categorical relationships were examined using Pearsons Chi-squared test with Yates continuity correction 1) DNA/RNA extration: Extensive optimization 2) LC, Hybrid Capture: Extensive optimization 3) Analysis pipeline: Advance computational biology 4) Clinical report: Resource intensive 1）DNA / RNA提取：广泛的优化 2）LC，杂交捕获：广泛的优化 3）分析管道：提前计算生物学 4）临床报告：资源密集型 Comparison of available clinical and molecular characteristics of METex14 NSCLC patients with or without concurrent MET amplification High magnification HE stained image of a metastatic lesion in a mediastinal lymph node showing retraction artifact seen in tumors with micropapillary features Post 2 months of neo-adjuvant crizotinib high magnification image showing extensive fibrosis in the resected primary lung tumor Diverse targetable METex14 alterations were identified in NSCLC patients across age groups,including elderly patients,and i