Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle

Examples of Oncogenic RNA Viruses (from Ruddon, 3rd Ed, Table 6.2) Acute Transforming Viruses Rous Sarcoma (non-defective)Chicken Sarcoma Avian Erythroblastosis Chicken Leukemia Avian MyeloblastosisChicken Leukemia Avian MyelocytomatosisChicken Abelson LeukemiaMouse Leukemia Harvey SarcomaRat Sarcoma Kirsten SarcomaRat Sarcoma Feline SarcomaCat Sarcoma Simian SarcomaMonkey Sarcoma RNAOnc1

Examples of Oncogenic RNA Viruses Acute Transforming Viruses What Genetic Information Makes Them Oncogenic? Rous Sarcoma Chicken Sarcoma Avian ErythroblastosisChicken Leukemia Avian MyeloblastosisChicken Leukemia Avian MyelocytomatosisChicken Abelson LeukemiaMouse Leukemia Harvey SarcomaRat Sarcoma Kirsten SarcomaRat Sarcoma Feline SarcomaCat Sarcoma Simian SarcomaMonkey Sarcoma Extra Gene src erb myb myc abl Ha-ras Ki-ras fms sis RNAOncG1

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Table 4.1 The Biology of Cancer (© Garland Science 2007). P. 100

Cell Site-of-action of Onc-Gene Products (from Scientific American) sis OncLocus

Site of Action of Onc-Gene Products Nucleus myc (N-myc, C-myc, L- myc) myb fos ski jun erb-A Receptor Tyr Kinases erb-B (EGF Receptor) erbB-2/neu (her-2/neu) met fms kit trk Non-receptor Tyr-Kinase abl src Ser/Thr Kinases raf PKC (Protein Kinase C) GTP-Binding Proteins Ha-Ras N-Ras K-Ras Growth Factors sis int-2 hst Others B-lym T-lym-1 bcl-1 (Cyclin D1) bcl-2 OncSite

Questions About V-Onc Genes Affecting the Biology of Cancer Where Does A Virus Get It From? How Many Different V-Onc Genes Exist? What Protein Does Each Code For? What Do Those Proteins Do? Where Do Those Proteins Do Their Thing? Why Do They Cause Transformation? How Do They Cause Transformation? Do They Have a Normal function? What Do They Tell Us About Neoplastic Transformation Not Involving V-Onc Genes? OncQues1

Alternative Ways in Which Oncogenes Transform Cellular Gene Expression v-Onc Gene Insertion (Acutely Transforming Retrovirus) Activation of c-onc Genes (Sub-acutely transformingretroviruses and DNA viruses) Mutations in c-onc Genes Gene Rearrangements and Gene Fusions Involving c-Onc Genes Amplification of c-Onc Genes TransWay

Figure 4.2 (part 1 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Transfection of DNA from Transformed Cells into Normal Mouse Fibroblasts:

Figure 4.2 (part 2 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Determination of Transforming Ability of Transfected DNA Fragments

Figure 4.10 The Biology of Cancer (© Garland Science 2007) Point Mutation Affecting Amino Acid 12 (Glycine) in H-RAS Gene Product in Human Bladder Cancer

Table 4.2 The Biology of Cancer (© Garland Science 2007) p. 106

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Figure 4.11b The Biology of Cancer (© Garland Science 2007) p. 107 Amplification of Endogenous c-Oncogene in Human Cancer: N-Myc in Human Neuroblastoma.

Table 4.4 The Biology of Cancer (© Garland Science 2007) p. 111

Figure 4.15a The Biology of Cancer (© Garland Science 2007) p. 113 Translocation and Chromosome Fusion in the Activation of Endogeneous C-Oncogenes

Figure 4.15b The Biology of Cancer (© Garland Science 2007) p. 113 Fusion Oncoproteins in Human Malignancies; Bcr-Abl Fusion Proteins C-Abl part CNL = Chronic neutrophilic leukemia

Table 4.5 The Biology of Cancer (© Garland Science 2007) p. 114

Questions About c-Onc Genes Affecting Prevention, Diagnosis, and Treatment of Clinical Cancers Can We Prevent Neoplastic Transformation Based on Oncogene Effects? Can We Use Oncogene Expression for Diagnosis and Prognosis? Can We Tailor Existing Treatments Based on Oncogene Expression in a Patient? Can We Develop New Treatments Based on the Biochemistry of Oncogene Products ? OncQues2

c-Onc Genes Not Defined by V-Onc Gene Transfection from Viruses c-Onc Genes Perturbed by retrovirus integration int-1 Mouse mammary tumor virus int-2 Mouse mammary tumor virus MLV1-1 Murine Leukemia Virus Rat MLV1-2 Murine Leukemia Virus Rat Pim-1 Murine Leukemia Virus Rat c-Onc Genes Detected by DNA Transfection N-ras Neuroblastoma/leukemia/sarcomas B-lym B-cell lymphoma mam Mammary carcinomas neu Neuroblastoma/glioblastoma cOncFind