1. Chapter 3: Tumor Viruses Peyton Rous discovers a chicken sarcoma virus (1911)

2. Rous sarcoma virus is discovered to transform infected cells in culture Retrovirus Renato Dulbecco (California IT) Harry Rubin/ An RSV-induced focus Howard Temin/ Transformation Howard Temin, 1975 Nobel Prize with David Baltimore

3. Transformed cells forming foci.

4. The continued presence of RSV is needed to maintain transformation

5. Shope papillomavirus Viruses containing DNA molecules are also able to induce cancer SV40 virus Permissive host Polio vaccine (Sabin and Salk) contaminated with SV40 from 1955 to 1963

6. Anchorage-independent growth Nude mice Tumor viruses induce multiple changes in cell phenotype including acquisition of tumorigenicity Transformation

7. Tumor virus genomes persist in virus-transformed cells by becoming part of host-cell DNA Almost all cervical cancer found HPV genome

8. The life cycle of an RNA tumor virus like RSV.

9. A version of the src gene carried by RSV is also present in uninfected cells Structure of the RSV genome

10. The construction of a src-specific DNA probe.

11. RSV exploits a kidnapped cellular gene to transform cells Proto-oncogene

12. The vertebrate genome carries a large group of protooncogenes

14. Slowly transforming retroviruses activate protooncogenes by inserting their genomes adjacent to these cellular genes Some retroviruses naturally carry oncogenes Insertional mutagenesis ALV/ lack acquired oncogenes B-call lymphomas induced by ALV HTLV-I/ tax (transcription activator)

16. Chapter 4: Cellular Oncogenes Can cancers be triggered by the activation of endogenous retroviruses? Transfection of DNA provides a strategy for detecting nonviral oncogenes Transfection

17. Transformation of mouse cells by human tumor DNA

18. Oncogenes discovered in human tumor cell lines are related to those carried by transforming retroviruses Homology between transfected and retroviral oncogenes. ×

20. Amplification of the erbB2/HER2/neu oncogene in breast cancers Fluorescence in situ hybridization Kaplan-Meier plot

21. Elevated expression of 17q genes together with overexpression of rebB2/HER2

22. Nonrandom amplifications and deletions of chromosomal regions

23. Proto-oncogenes can be activated by genetic changes affecting either protein expression or structure Cloning of transfected human oncogenes

24. Localization of an oncogene-activating mutant transfection-focus assay

25. Mutation responsible for H-ras oncogene activation Concentration of point mutations leading to activation of the K-ras oncogene

27. Variations on a theme: the myc oncogene can arise via at least three additional distinct mechanisms N-myc amplification and neuroblastoma Gene myc MYC Protein Myc MYC

29. Burkitt’s lymphoma incidence in Africa Chromosomal translocations in Burkitt’s lymphoma

31. Translocations liberating an mRNA from miRNA inhibition

32. A diverse array of structural changes in proteins can also lead to oncogene activation Deregulated firing of growth factor receptors

33. Formation of the bcr-abl oncogene