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what is the difference between oncogenes and tumor suppressor genes oncogenes - promote cell growth tumor supressor genes - restrict cell growth -what are the number of mutations required for oncogenes vs TS genes -what is the function of the mutant allele (loss or gain of function) -what is the origin of the mutation -give an example oncogenes- 1 mutation (dominant), gain of function, somatic, protein kinase TS genes- 2 mutations (recessive), loss of function, inherited or somatic, transcription factor what is somatic cell activation of proto-oncogenes in human neoplasia by DNA arrangement tumor specific breakpoints reveal mechanisms of tumorogenesis t(9,22) found in chronic mylogenous leukemia oncogene on 9q (ABL) is translocated to chromosome 22(BCR) so that the oncogene is always on what is the drug that can be used to treat chronic mylogenous leukemia. what does this target glevig - targets tyrosine kinase describe the mechanism and disease caused by t(8,14) to an active chromatin domain C-myc (on 8) is transferred to 14 so that is always on - Burkitts lymphoma what is somatic cell activation of proto-oncogenes in human neoplasia by DNA amplification many cancer cells contain multiple copies of normal oncogenes in the form of: double minutes: c-myc in leukemia insertions: homogenous staining regions (neuroblastoma) what is somatic cell activation of proto-oncogenes in human neoplasia by DNA point mutation point mutations leading to altered amino acids many point mutations found in RAS in tumors found throughout the body what are tummor suppressor genes and what is there role in hereditary disposition to some human cancers TP53(17p12)- gatekeeper that keeps oncogenic cells or cells with damaged DNA from progressing to S phase commonest region for loss of heterozygosity Li Fraumeni what is the knudson hypothesis two successive mutations are required to turn a normal cell line into a cancer cell line RB- 60% are sporadic 40% - inherited two mutations must be acquired for tumor surpressor genes what are mismatch repair genes fix errors in DNA replication mutation leads to genomic instability what is the role of mismatch repair genes in multi-step molecular genetic models for carcinogenesis mutation leads to inefficient replication and repair of DNA tumor cells typically have multiple structural and numerical abnormalities recessive- require 2 hits what are the 6 specific capabilities a cell acquires to transform from a normal cell to a malignant cancer cell 1. independent of external growth signals 2. insensitive to external anti-growth signals 3. avoid apoptosis 4. continual replication 5. angiogenesis 6. tissue invasion and metastasis what are two tumor cells that have multiple structural and numerical chromosomal abnormalities familial adenomatous polyposis hereditary nonpolyposis colon cancer what are three mechanisms an individual who is heterozygous for RB, can loose this heterozygosity 1. interstitial deletion 2. point mutation 3. recombination 4. loss of chromosome how can recombination lead to loss of heterozygosity of RB somatic recombination can lead to one cell line containing both alleles for RB, and the other cell line carrying both alleles for wt gene what are the three goal of cancer genetics 1. assist in dx, provide therapy guidance, and prognosis info 2. monitor remession and relapse 3. identify genes in tumorigenesis