1. Copyright © 2009 Pearson Education, Inc. Essentials of Genetics Seventh Edition Klug, Cummings, Spencer, Palladino Chapter 16 Cell Cycle Regulation and Cancer Copyright © 2009 Pearson Education, Inc.

2. Table 20.1 16.1Cancer Is a Genetic Disease That Arises at the Level of Somatic Cells

3. Copyright © 2009 Pearson Education, Inc. Figure 16.1a Spectral karyotype of a normal cell

4. Copyright © 2009 Pearson Education, Inc. Figure 16.1b Spectral karyotype of a cancer cell, showing translocations, deletions, and aneuploidy.

5. Copyright © 2009 Pearson Education, Inc.

6. 16.1Cancer Is a Genetic Disease What Is Cancer?  Not a single disease  Vary in age of onset, growth rates, invasiveness, prognoses, and response to treatment.  At molecular level, all cancers exhibit common characteristics  Cell Proliferation = Abnormal cell growth and division  Metastasis = Abnormalities in normal restraints that keep cells from spreading and invading other body parts.

7. Copyright © 2009 Pearson Education, Inc. 16.1Cancer Is a Genetic Disease The Clonal Origin of Cancer Cells  All cancer cells are clonal  Originated from common ancestral cell that accumulated specific mutations.

8. Copyright © 2009 Pearson Education, Inc. 16.1Cancer Is a Genetic Disease Cancer As a Multistep Process, Requiring Multiple Mutations  A single mutation is not sufficient to transform a normal cell into a tumor forming, malignant cell.  Mutations in humans occur randomly at a rate of 10 10 mutations per gene in the body during their lifetime.  Incidence of cancer rises exponentially with age.  Many independent mutations, occurring randomly, are necessary before a cell becomes malignant.  Delay occurs between exposure to carcinogens and the appearance of cancer.

9. Copyright © 2009 Pearson Education, Inc. Figure 18-2 Copyright © 2006 Pearson Prentice Hall, Inc.

10. Copyright © 2009 Pearson Education, Inc. 20.2Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair and Chromatin Modifications Genomic Instability and Defective DNA Repair Cancer cells show higher than normal rates of mutation, chromosomal abnormalities, and genomic instability. Cancer cells grown in cultures show a great deal of genomic instability Cancers show specific defects that are used to diagnose the type and stage of cancer.

11. Copyright © 2009 Pearson Education, Inc. DNA amplification in neuroblastoma Cancer genes are colored and remain separate from chromosomal DNA. Red = MYCN Green = MDM2 Blue = normal

12. Copyright © 2009 Pearson Education, Inc. Multiple copies of the MYCN gene are amplified in the green staining region; single copies are seen as the small green dots; normal chromosomes are stained red.

13. Copyright © 2009 Pearson Education, Inc. Figure 20.3

14. Copyright © 2009 Pearson Education, Inc. Thursday, November 6, 2008 Scientists Decode Set of Cancer Genes By DENISE GRADYDENISE GRADY Published: November 5, 2008 For the first time, researchers have decoded all the genes of a person with cancer and found a set of mutations that may have caused the disease or aided its progression. Using cells donated by a woman in her 50s who died of leukemia, the scientists sequenced all the DNA from her cancer cells and compared it to the DNA from her own normal, healthy skin cells. Then, they zeroed in on 10 mutations that occurred only in the cancer cells, apparently spurring abnormal growth, preventing the cells from suppressing that growth and enabling them to fight off chemotherapy.cancer chemotherapy

15. Copyright © 2009 Pearson Education, Inc. NYTimes article on new teatment

16. Copyright © 2009 Pearson Education, Inc. 16.2Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair and Chromatin Modifications Chromatin Modifications and Cancer Epigenetics  Epigenetics is the heritable changes that occur to DNA without affecting the nucleotide sequence of DNA.  Cancer cells contain DNA with major methylation alterations  Histone modifications lead to packaging issues related to DNA organization.

17. Copyright © 2009 Pearson Education, Inc. 16.3Cancer Cells Contain Genetic Defects Affecting Cell-Cycle Regulation The Cell Cycle and Signal Transduction

18. Copyright © 2009 Pearson Education, Inc. Cyclins and cyclin-dependent kinases (CDKs) control progress through the cell cycle.

19. Copyright © 2009 Pearson Education, Inc. 16.3Cancer Cells Contain Genetic Defects Affecting Cell-Cycle Regulation Control of Apoptosis  Programmed cell death  If mistakes are not corrected during progression through the cell cycle, apoptosis must occur.  Nuclear DNA becomes fragmented, the cell dissolves, and phagocytic cells engulf and destroy.  Apoptosis reduces the number of mutations that are passed to the next generation.

20. Copyright © 2009 Pearson Education, Inc. Figure 20.8

21. Copyright © 2009 Pearson Education, Inc. 16.4Many Cancer-Causing Genes Disrupt Control of the Cell Cycle

22. Copyright © 2009 Pearson Education, Inc. 16.4Many Cancer- Causing Genes Disrupt Control of the Cell Cycle The ras Proto-oncogenes

23. Copyright © 2009 Pearson Education, Inc. Figure 18-12 Copyright © 2006 Pearson Prentice Hall, Inc.

24. Copyright © 2009 Pearson Education, Inc. 16.4Many Cancer-Causing Genes Disrupt Control of the Cell Cycle The cyclin D1 and cyclin E Proto-oncogenes The p53 Tumor-Suppressor Gene The “guardian of the genome” The RB1 Tumor-Suppressor Gene

25. Copyright © 2009 Pearson Education, Inc. Figure 20.10

26. Copyright © 2009 Pearson Education, Inc. Figure 20.11

27. Copyright © 2009 Pearson Education, Inc. Predisposition to Some Cancers Can Be Inherited

28. Copyright © 2009 Pearson Education, Inc. 20.7Viruses Contribute to Cancer in Both Humans and Animals

29. Copyright © 2009 Pearson Education, Inc. Figure 20.13

30. Copyright © 2009 Pearson Education, Inc. 20.8Environmental Agents Contribute to Human Cancers Obesity responsible for 100,000 cancer cases annually By Matt Sloane, CNN Medical News November 5, 2009 5:58 p.m. EST