复旦大学：《医学遗传学 Medical Genetics》课程教学资源（PPT课件讲稿）Cancer genetics

Medical genetics Cancer genetics Yongbo wang(王勇波) 2014-12-26 Department of Cellular and Genetic Medicine, Schoolof Basic Medical Sciences, Fudan University

Yongbo Wang（王勇波） 2014-12-26 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University Cancer Genetics Medical genetics

Outline 1. What Is Cancer? Introduction of the basic concepts 2. What Causes Cancer? a Genetic underpinnings of cancer Three types of Cancer Critical Genes Cancer initiation and progression 3. How to Prevent and Diagnose Cancer? Utilization the knowledge we learned from cancer genetIcs

1. What Is Cancer? ◼ Introduction of the basic concepts 2. What Causes Cancer? ◼ Genetic underpinnings of cancer ◼ Three types of Cancer Critical Genes ◼ Cancer initiation and progression 3. How to Prevent and Diagnose Cancer? ◼ Utilization the knowledge we learned from cancer genetics Outline

What Is cancer Cancer is the most virulent disease and soon becoming the leading cause of death worldwide: as many as ca. 1 in 3 individuals develop cancer and 1 in 4 will die of it Percentage of all deaths due to five leading causes of death by year United States 1935-2010) All other causes Stroke Accidents(unintentional injuries) Influenza and pneumonia Certain diseases of early infancy Kidney disease Heart disease Chronic lower respiratory diseases 100 it 9351940 1970 1980 990 2000 NOTE: 2010 data are preliminary SOURCE: CDC/NCHS, National Vital Statistics System, Mortality http://www.cdc.gov/nchs/data/databriefs/db88.htm

◼ Cancer is the most virulent disease and soon becoming the leading cause of death worldwide: as many as ca. 1 in 3 individuals develop cancer and 1 in 4 will die of it. 1. What Is Cancer? (Percentage of all deaths due to five leading causes of death by year: United States, 1935–2010.) http://www.cdc.gov/nchs/data/databriefs/db88.htm

An abnormal cell that grows and proliferates out of control will give rise to tumor or neoplasm. Benign: as long as the tumor cells do not become Invasive Malignant: tumor cells have acquired the a bility to invade surrounding tissues. a a tumor is considered a cancer only if it is malignant Metastasis: spread of malignant tumor cells throughout the body (typically through the blood and lymphatic system)

◼ An abnormal cell that grows and proliferates out of control will give rise to tumor or neoplasm. ◼ Benign: as long as the tumor cells do not become invasive; ◼ Malignant: tumor cells have acquired the ability to invade surrounding tissues. ◼ A tumor is considered a cancer only if it is malignant. ◼ Metastasis: spread of malignant tumor cells throughout the body (typically through the blood and lymphatic system)

There are a large variety types of cancer which are classified according to the tissue and cell type from which they derive: carcinoma(arising from epithelial cells), sarcoma (from connective tissue or muscle cells), leukemia and lymphoma (from hemopoietic cells), cancers derived from cells of nervous system etc EPITHELIUM=> CARCINOMA (About 80%of human cancers Basal Lamina Collagen MESENCHYMAL ORIGIN >SARcoMA … fibro|asts … blood vessels blood cells muscle … adipocytes(fat) bone car tilage

◼ There are a large variety types of cancer which are classified according to the tissue and cell type from which they derive: carcinoma (arising from epithelial cells), sarcoma (from connective tissue or muscle cells), leukemia and lymphoma (from hemopoietic cells), cancers derived from cells of nervous system etc. (About 80% of human cancers)

Example: development of cancer of the epithelium of the uterine cervix LOW-GRADE HIGH-GRADE NORMAL EPITHELIUM INTRAEPITHELIAL INTRAEPITHELIAL INVASIVE CARCINOMA NEOPLASIA NEOPLASIA 〓Me=g2 (C) (D) Benign Malignant Adapted from Molecular Biology of the Ce// 5th edition

Adapted from Molecular Biology of the Cell 5th edition Example: development of cancer of the epithelium of the uterine cervix Benign Malignant

Cancer originating from different origin are, in general very different diseases oral cavI and pharynx digestive organs cancers of respiratory epithelia system carcinomas reproductive urinary kin melanoma leukemias and lymphomas ste KEYA new cases deaths/year connective tissue, other 200 300 number per year (thousands) Incidence and mortality of different cancers in the United States. Data from American Cancer Society, 2004 Adapted from Molecular Biology of the Ce// 5th edition

◼ Cancer originating from different origin are, in general, very different diseases. Incidence and mortality of different cancers in the United States. Data from American Cancer Society , 2004. Adapted from Molecular Biology of the Cell 5th edition

Part 1 summary 1). The basic concepts Benign and malignant tumor Cancer cells reproduce without restraint and colonize other tissues 2). Cancer is a very complex and virulent disease Cancer is becoming the leading cause of death worldwide a There are large variety kinds of cancer which can be classified by their tissue or cell origin Different types of cancer can be considered as very different disease

Part 1 summary 1). The basic concepts ▪ Benign and malignant tumor ▪ Cancer cells reproduce without restraint and colonize other tissues 2). Cancer is a very complex and virulent disease ▪ Cancer is becoming the leading cause of death worldwide. ▪ There are large variety kinds of cancer which can be classified by their tissue or cell origin. ▪ Different types of cancer can be considered as very different disease

2. What Causes Cancer Chemical Exposure Behavior(Tobacco smoke -> lung cancer) Environmental (polychlorinated biphenyl,(PCBs) Occupational (coal tar, asbestos aniline dye) Diet (aflatoxin-> liver cancer Radiation(UV-> Xeroderma pigmentosum, ionizing Infection Viruses(Epstein-Barr virus(EBv)-> lymphoma, hepatitis B->liver cancer, papilloma-> cervical cancer etc) Inherited familial cancer syndromes Mutations and or chromosomal abnormalities Most, if not all, of these causes have their genetic underpinning linked with cancer

2. What Causes Cancer? • Chemical Exposure – Behavior (Tobacco smoke -> lung cancer) – Environmental (polychlorinated biphenyl, (PCBs)) – Occupational (coal tar, asbestos, aniline dye) – Diet (aflatoxin -> liver cancer) • Radiation (UV -> xeroderma pigmentosum,ionizing) • Infection – Viruses (Epstein–Barr virus (EBV) -> lymphoma, hepatitis B -> liver cancer, papilloma -> cervical cancer etc) • Inherited familial cancer syndromes • Mutations and/or chromosomal abnormalities Most, if not all, of these causes have their genetic underpinning linked with cancer

Aflatoxin b can directly reacting with on DNA and induce mutations Is a toxin from mold that grows on grain and peanuts when stored in humid tropical conditions and a contributory cause of live cancer in the tropics with a characteristic mutations in TP53 OH cytochrome P-450 OCH OCH H2N DNA AFLATOXIN AFLATOXIN-2, 3-EPOXIDE CARCINOGEN BOUND TO GUANINE IN DNA Figure 20-22a Molecular Biology of the Cell 5/e(o Garland Science 2008)

◼ Aflatoxin B can directly reacting with on DNA and induce mutations - Is a toxin from mold that grows on grain and peanuts when stored in humid tropical conditions; - and a contributory cause of live cancer in the tropics with a characteristic mutationsin TP53