chapter_9 - Cancer genetics cancer development depends on...

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Tissue homeostasis comprises strictly supervised cellular processes. Disruption of any of these processes can ultimately result in the formation of a tumor. Depending on the prominent disturbed cellular process, malignant cells will display different features. In malignancies in which development is halted at an early stage malignant cells will display immature features, including a high proliferative potential. When extensive differentiation stands out the neoplastic clone will present a more mature phenotype (although these cells will be functionally defective). Deficient apoptosis as well, can contribute to malignant transformation. cancer development is a multi step micro-evolutionary process Numerous experiments have unequivocally demonstrated that the acquisition of a single genetic defect, or mutation, is necessary, however not sufficient to cancer development. Above all the genetic model of colorectal cancer has been helpful in our understanding of cancer development in general. Colorectal cancer develops from essentially benign lesions to invasive cancer as a result of the accumulation of mutations in different genes, tumor suppressors as well as oncogenes. In this respect it is noteworthy that cancer development is subject to evolutionary changes: clonal expansion drives the accumulation of different mutations which are selected for whenever they provide substantial benefit to the outgrowth of the tumor. Quite remarkably, as demonstrated in the genetic model of colorectal cancer, the sequence of mutation acquisition is far from random. Arguably, identical gene mutations provide a similar benefit for clonal expansion at comparable stages of tumor development. The acquisition of several genetic defects in a cancerous cell, allows it to take on numerous processes from which it would normally be excluded. These characteristic properties include: autonomous and limitless growth, invasion and metastasis. normal and malignant hematopoiesis Despite the functional and morphological diversity displayed by the different cellular constituents of the peripheral blood and the lymphoid organs, compelling evidence suggests that all these cells are the progeny of a single cell type, the hematopoietic stem cell (HSC). Normal hematopoiesis, literally blood formation, refers to the process in which these pluripotent HSCs differentiate into either of the various known hematological cell types.The primary site of action of the HSCs is the bone marrow. HSCs display unique characteristics, conserving an immature phenotype, allowing them to differentiate into a wide variety of cells and in addition maintaining the property of self-replication, resulting in sustained hematopoiesis throughout the entire lifespan of the individual. Cancer genetics
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This note was uploaded on 05/28/2010 for the course WE BIBI000000 taught by Professor Johangrooten during the Spring '10 term at Ghent University.

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chapter_9 - Cancer genetics cancer development depends on...

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