Hereditary Cancer Syndromes Marek Svoboda Masaryk Memorial Cancer Institute & Faculty of Medicine, Masaryk University Human Genome Milestones from the perspective of cancer genetics 1866 – Gregor Mendel, Brno, Mendelian inheritance 1953 – DNA structure (Nature, Watson, J.D., Crick, F.H ) 1974 – Knudson AG, study of retinoblastomas: “two-hit hypothesis“ 1982 – identification of the first human oncogenes „H-ras“ a „K-ras“ 1987 – identification of the Rb1 tumor supresor gene 1999 – Fearon-Vogelstein´s evolutionary model of carcinogenesis 2000 –„the next generation sequencing“ (DNA sequencers on the market) 2001 –„the draft“ of the human genome (Nature and Science) 2003 – the Human Genome Project finished the human genome sequence (ca 30 000 genes) C:\Documents and Settings\Administrator\Dokumenty\Obrázky\1953_2003.jpg Hereditary Cancer Syndromes draft – nárys, skica Basic Dogmas of Oncology Genetic information DNA ® RNA Molecular structure of protein Biochemical function of protein Symptoms (Phenotype) Aberrant gene expression is a key step in the initiation, promotion and progression of the tumor III) Biological correlates of gene expression are identifiable I) Cancer is a genetic disease Hereditary Cancer Syndromes II) Carcinogenesis is a multistep process Carcinogenesis is a multistep process involving alterations in at least two distinct classes of genes použití dna čipů v diagnostické a prdiktivní onkologii se odvíjí od několika základních předpokladů Hereditary Cancer Syndroms Hereditary Cancer Syndromes Rb1, p53, p21 Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes IDENTIFYING AT-RISK PATIENTS Hereditary Cancer Syndroms Hereditary Cancer Syndromes ovarian ca 53 yo breast ca 45 yo breast ca 34 yo ovarian ca 45 yo prostate ca 45 yo Hereditary Cancer Syndroms Hereditary Cancer Syndromes SELECT AND OFFER TEST Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes > Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes Hereditary Cancer Syndroms Hereditary Cancer Syndromes