Gcd 3022 1st edition Lecture 37 Outline of Last Lecture I Genetic basis of cancer a Characteristics b Statistics II Viruses that cause cancer a Efficiency of causing cancer b Acutely transforming viruses c Rous sarcoma virus III Oncogenes a Development b Patterns of expression c Conversion of proto oncogenes i Missense mutation ii Gene amplification iii Chromosomal locations iv Viral integration IV Tumor suppressor genes a Inactivation of tumor suppressor genes i Mutation in gene itself ii DNA methylation iii Aneuploidy b Genome maintenance i Checkpoint proteins ii Cyclins and cyclin dependent kinases iii DNA repair enzymes c p53 gene i Functions ii Apoptosis d Retinoblastoma i Two types ii Two hit model V Multiple genetic changes a Development pattern of cancers b Colorectal cancer study c Genetic changes leading to cancer VI Inherited forms of cancers These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute a Predisposition for developing cancer b Loss of heterozygosity Outline of Current Lecture I Locus heterogeneity II Formation of cancer a Proto oncogenes b Transformation c Causes of cancer d Accumulation of mutations e Missense mutation f Retinoblastoma III Stages of cancer progression IV Patterns of inheritance a Inherited cancers b Haploinsufficiency c Concordance Current Lecture I Locus heterogeneity a situation where people with the same phenotype have different genotypes II Formation of cancer a Proto oncogenes not usually involved in inherited forms of cancer because mutations that occur in these genes are gain of function mutations which would be exhibited in the development of the embryo and could result in fatality Most inherited forms of cancer typically contain mutations in tumor suppressor genes not proto oncogenes b Transformation can refer to the process of introducing DNA into prokaryotic cells by chemical or physical means or the process that results in conversion of a normal cell into a cancer cell c Causes of cancer mutation to tumor suppressor gene loss of function mutation reduced function of tumor suppressor gene point mutations increase in the copy number of the proto oncogene or a change in the relationship between a coding region and regulatory elements of the proto oncogene d Accumulation of mutations cancer cells are more likely than normal cells to accumulate mutations over time because they are allowed to divide despite potential errors in DNA synthesis e Missense mutation the missense mutation in ras that contributes to cancer decreases the GTPase activity of ras so that it is always in the on position leading to constitutive downstream signaling f Retinoblastoma a tumor in the retina can be inherited and form early in life or develop spontaneously later in life Both types of retinoblastoma require two mutations to occur III IV to the same cell two hit model People with the inherited disease already have one mutation which is why they develop the condition earlier in life Stages of cancer progression begins a normal cell that acquires at least one mutation that converts it to a tumor cell This cell divides to form a benign growth Additional genetic changes may occur to these cells that result in an invasive tumor called a malignant tumor The cells can then metastasize to other parts of the body Cancer is considered clonal because the growth originates from one cell Patterns of inheritance a Inherited cancers usually occur from the mutation of a tumor suppressor gene loss offunction mutation and follow the two hit model These tumor suppressor genes are responsible for allowing cell division under appropriate conditions b Haploinsufficiency the phenomenon where half of the normal amount of gene product is not sufficient to produce a wild type phenotype This type of mutation can play a role in how tumor suppressor genes contribute to cancer because it is a loss of function mutation c Concordance the degree to which identical twins and fraternal twins share the same trait A high rate of concordance would be indicated by the finding that identical twins share the same traits and fraternal twins are no more similar than other siblings If fraternal and identical twins show the same degree of concordance it is more likely that the trait is not determined solely by genetics
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