医学遗传学 16肿瘤遗传学eng v(0002)

2020/8/22
2020/8/22
Tumors are hereditary Hereditary retinoblastoma is an autosomal
dominant trait in which susceptibility to retinoblastoma is inherited. This is an unusual "dominant" trait in that a mutation in one RB gene is not sufficient to cause symptoms, but mutations in the second allele often arise during development.
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Growth factors These oncogenes produce factors that
stimulate cells to grow. The best known of these is called sis. It leads to the overproduction of a protein called plateletderived growth factor, which stimulates cells to grow.
2020/8/22
2020/8/22
Offspring have a 50% chance of receiving the mutant gene from a heterozygous parent, and 90% of carriers will develop retinoblastoma, usually in both eyes. The hereditary form is also associated with a high risk for other cancers especially of the bone and fibrous tissues (osteosarcomas and fibrosarcoma.
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Growth factor receptors These are normally turned "on" or
"off" by growth factors. When they are "on," they stimulate the cell to grow. Certain mutations in the genes that produce these cause them to always be "on." In other cases, the genes are amplified.
The mutations occur after birth and result in tumor formation. Tumors usually develop in only one eye and patients are not at high risk for other cancers. Both alleles need to be mutated in a single cell, and that is why this form typically occurs only in one eye.
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Sporadic retinoblastoma is a trait in which the affected individual has not inherited any mutant alleles of the retinoblastoma gene.
2020/8/22
2020/8/22
2020/8/22
Chromosome and tumors Detailed studies of the Philadelphia chromosome
show that most of chromosome 22 has been translocated onto the long arm of chromosome 9. In addition, the small distal portion of the short arm of chromosome 9 is translocated to chromosome 22. This translocation, which is found only in tumor cells, indicates that a patient has chronic myelogenous leukemia (CML). In CML, the cells that produce blood cells for the body (the hematopoietic cells) grow uncontrollably, leading to ca for normal cell growth starts with growth factor, which locks onto a growth factor receptor. The signal from the receptor is sent through a signal transducer. A transcription factor is produced, which causes the cell to begin dividing. If any abnormality is detected, the cell is made to commit suicide by a programmed cell death regulator.
16 遗传与肿瘤发生 Cancer Genetics
2020/8/22
The ancient Greeks believed that cancer was caused by too much body fluid they called "black bile."
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Doctors in the seventeenth and eighteenth centuries suggested that parasites caused cancer. Today, doctors understand more about the link between cancer and genetics.
2020/8/22
2020/8/22
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The connection between this chromosomal abnormality and CML was clarified by studying the genes located on the chromosomes at the sites of the translocation breakpoints.
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It may be helpful to think of a cell as a car. For it to work properly, there need to be ways to control how fast it goes. A proto-oncogene normally functions in a way that is similar to a gas pedal -- it helps the cell grow and divide. An oncogene could be compared to a gas pedal that is stuck down, which causes the cell to divide out of control.
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Proto-oncogenes are the genes that normally control how often a cell divides and the degree to which it differentiates (or specializes). When a proto-oncogene mutates (changes) into an oncogene, it becomes permanently "turned on" or activated when it is not supposed to be. When this occurs, the cell divides too quickly, which can lead to cancer.
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For the most part, cancer arises from a single cell, that is, cancer is a clonal disease. The average human being contains about 1014 cells (i.e., 100,000,000,000,000 cells), any one of which could, in principle, become a cancer cell, if it acquired the right sort of mutations while it still had the potential to proliferate.
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In one of the translocated chromosomes, part of a gene called abl is moved from its normal location on chromosome 9 to a new location on chromosome 22. This breakage and reattachment leads to an altered abl gene. The protein produced from the mutant abl gene functions improperly, leading to CML.