个体化治疗分类.PPT

* * Permission to include this figure in this CCO activity was granted by Daniel J. Sargent, PhD. * Permission to include this figure in this CCO activity was granted by Daniel J. Sargent, PhD. * 78份乳腺癌样品，70个基因进行聚类。 * 对于上面挑选的70个基因，用另外19份样品进行验证 * 个体化医疗常用的方法 免疫组化和核酸杂交（FISH，KISH） 荧光定量PCR 测序 STR扫描 芯片 DNA测序 DNA测序囊括了确定DNA寡核苷酸上碱基顺序的生化方法。DNA测序技术的出现显著加速了生物学研究和发现的进程。 “DNA测序被认为是序列分析的模板和参考（有时也被称为是“金标准”） Class II Special Controls Guidance for CFTR Gene Mutation Detection Systems, Pharmacogenetic Tests and Genetic Tests for Heritable Markers Guidance. FDA a 测序技术应用于临床已获得美国FDA的认可 测序技术用于临床在中国已具备的条件 2008年4月测序仪获得SFDA医疗器械注册证 各省市均有测序的收费物价 上海：　600元 江苏： 600元 浙江： 600元 重庆： 380元 湖南：　300元　 测序技术用于临床在中国已具备的条件 2009年3月测序试剂盒获得SFDA医疗器械注册证 EGFR exon19 突变与易瑞沙反应性 EGFR exon20 突变与易瑞沙反应性 个体化医疗常用的方法 免疫组化和核酸杂交（FISH，KISH） 荧光定量PCR 测序 STR扫描 芯片 淋巴瘤分型诊断 正常淋巴结增生？ B淋巴瘤？ T淋巴瘤？ Deficient Mismatch Repair (dMMR) as a Marker in Stage II/III Colon Cancer Pooled analysis of data from patients with stage II disease enrolled in trials of 5-FU–based chemotherapy vs control (no treatment) MMR determined by MSI testing, if possible; dMMR = MSI high frequency/loss of MLH1 or MSH2 Proficient MMR = microsatellite stable/MSI + MSI low-frequency or normal protein expression Primary endpoint: DFS comparing 5-FU–based treatment with control by MMR status Secondary endpoint: OS Sargent DJ, et al. ASCO 2008. Abstract 4008. DFS by MMR Status (Pooled Data) HR: 0.79 (0.49-1.25) P = .30 HR: 0.51 (0.29-0.89) P = .009 Treated (N = 512) Untreated (N = 515) dMMR: 70% pMMR: 67% 5-Yr DFS dMMR: 80% pMMR: 56% 5-Yr DFS Sargent DJ, et al. ASCO 2008. Abstract 4008. Reproduced with permission. 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 Yrs Disease Free (%) 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 Yrs Disease Free (%) OS by Treatment, Stage II dMMR Patients HR: 3.15 (1.07-9.29) P = .03 n = 55 n = 47 Untreated: 93% Treated: 75% 5-Yr OS P value = .014 for treatment by MMR status interaction 0 10 20 30 40 50 60 70 80