Genetics of Gastrointestinal Neoplasia 张咸宁 zhangxianning@zju.edu.cn Tel:13105819271;88208367 Office: A709, Research Building 2012/04
Genetics of Gastrointestinal Neoplasia 张咸宁 zhangxianning@zju.edu.cn Tel：13105819271; 88208367 Office: A709, Research Building 2012/04
Learning Objectives 1.掌握结直肠癌为模型的恶性肿 瘤的多步骤发生模式。 2.了解APC等相关癌基因
Learning Objectives 1. 掌握结直肠癌为模型的恶性肿 瘤的多步骤发生模式。 2. 了解APC等相关癌基因
Required Reading Thompson &Thompson Genetics in Medicine,7hEd(双语版,2009) ●pp.396-401; O Clinical Case Studies-19 Hereditary Nonpolyposis Colon Cancer
Required Reading Thompson &Thompson Genetics in Medicine, 7th Ed （双语版，2009） ● pp.396-401； ● Clinical Case Studies-19 Hereditary Nonpolyposis Colon Cancer
MUTATION Mutations in Mutations disrupting Mutations affecting coding region RNA stabilit gene regulation RNA splicing Protein abnormal Protein structure normal Decreased Hb Hammersmith (if unstable->decreased amount) amount CAUSE OF DISEASE aE-thalassemias B-thalassemias Monosomies Increased Tumor-suppressor mutations Loss of protein function amount Hb Kempsey Achondroplasia the great majority) Trisomies Charcot-Marie- Toot Gain of function disease type 1A Novel property Many oncogenes (infrequent Inappropriate expression (wrong time, place) Ectopic or heterochronic expression (uncommon, except in cancer
Feature Tumor Suppressor Oncogenes G enes Function of normal Regulates cell growth Promotes cell growth version and proliferation; and proliferation some can induce apoptosis Mutation(at cell level) Recessive(both Dominant (only one copies of gene copy of gene mutated) inactivated) Effect of mutation Loss of function Gain of function Germline mutations Seen in most tumor Seen in only a few resulting in inherited suppressor genes oncogenes cancer syndromes
Feature Tumor Suppressor Genes Oncogenes Function of normal version Regulates cell growth and proliferation; some can induce apoptosis Promotes cell growth and proliferation Mutation (at cell level) Recessive (both copies of gene inactivated) Dominant (only one copy of gene mutated) Effect of mutation Loss of function Gain of function Germline mutations resulting in inherited cancer syndromes Seen in most tumor suppressor genes Seen in only a few oncogenes