What Is Cancer? Dr Anil Mohith Medical Oncologist g R 1 What Causes Cancer? Some viruses or bacteria Some chemicals Radiation Heredity Diet Hormones R 2 Different Kinds of Cancer Some common carcinomas: Lung Leukemias: Bloodstream Lymphomas: Lymph nodes Breast (women) Colon Bladder Prostate (men) Some common sarcomas: Fat Bone Muscle R 3 Loss of Normal Growth Control Normal cell division Cell Suicide or Apoptosis Cell damage— no repair Cancer cell division First mutation Second mutation Third Fourth or mutation later mutation R Uncontrolled growth 4 Example of Normal Growth Dead cells shed from outer surface Epidermis p Dividing cells in basal layer Cell migration Dermis R 5 The Beginning of Cancerous Growth Underlying tissue R 6 Invasion and Metastasis 1 Cancer cells invade surrounding tissues and blood vessels 2 Cancer cells are transported by the circulatory system to distant sites 3 Cancer cells reinvade and grow at new location R 7 Microscopic Appearance of Cancer Cells R 8 Normal Cell Communication Genes mRNA Cell divides Proteins Cell autodestructs R Some communications pathways 9 Cancer: A Communication Failure Colon Retinoblastoma, bone, bladder, lung, g breast Many y cancers Genes mRNA Proteins Sarcomas Leukemia, brain,, breast, stomach, lung Leukemia R Some neuronal tumors 10 Genes and Cancer Viruses Chemicals Radiation Heredity Chromosomes are DNA molecules R 11 Expression Changes With Cell Type Myosin mRNA Myocyte has both genes, but . . . Myosin gene Myocyte makes myosin mRNA and not immunoglobulin mRNA Lymphocyte has both genes, but . . . Immunoglobulin gene No immunoglobulin mRNA No myosin mRNA Myosin gene Immunoglobulin gene Lymphocyte makes immunoglobulin mRNA and not myosin mRNA R Immunoglobulin mRNA 12 Human Genome Project Chromosome X R 13 Examples of Dominantly Inherited Cancer Syndromes R 14 DNA Mutation DNA CA AG C T A A C T Normal gene CA AG C G A A C T Single base change CA A G G CG C T A A C T Additions C T CA A G A A C T Deletions R 15 Oncogenes Normal cell Cancer cell Mutated/damaged oncogene Normal genes regulate cell growth Oncogenes accelerate cell growth and d division di i i R 16 Tumor Suppressor Genes Normal genes prevent cancer Normal cell Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes R 17 p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis) R 18 DNA Repair Genes Normal DNA repair T C GA C Base pair mismatch No cancer TC T AC AG C T G TC TAC TCT AC AG C T G Cancer AG TG AG A T G No DNA repair R 19 Cancer Tends to Involve Multiple Mutations Benign tumor cells grow only locally and cannot spread by i invasion i or metastasis t t i Malignant cells invade neighboring tissues, enter blood vessels, and metastasize t t i to t different diff t sites it Time Mutation Cells inactivates proliferate suppressor gene Mutations inactivate DNA repair genes Proto-oncogenes mutate to oncogenes More mutations, more genetic instability, metastatic disease R 20 Example: Translocation of Bcr-Abl Genes 9 9 (q+) Ph 22 bcr (22q–) bcr-abl abl Fusion protein with tyrosine kinase activity R 21 Molecular Diagnostics Old Way Patient’s tissue sample Pathology Proteomics Proteins New Way Mass spectrometry Proteomic image Genomics Patient’s tissue sample or blood sample R DNA Gene chip Microarray image 22 THANK YOU R 23