Tumor chromosomal translocations

The presence of chromosomal translocations is a consistent feature of many leukemia s, lymphomas, and certain solid tumors. At the genetic level, these events can either deregulate an intact gene by disruption or removal and replacement of the adjacent controlling elements, or create a new fusion gene that express the N-terminus of one protein fused to the C-terminus of another protein. 

Like many other nonreceptor tyrosine kinases, Abl tyrosine kinase may be converted by mutations into a dominant oncoprotein and thus contribute to tumor formation. Abl tyrosine kinase was first discovered as the oncogene of murine Abelson leukemia virus. Chronic myelogenic leukemia in humans is cause by a chromosome translocation in which a fusion protein is created of Abl tyrosine kinase and a Bcr protein (c Chapter 14). The result is a greatly increased tyrosine kinase activity, to which a causal role in occurrence of this leukemia is attributed. 

A distinction is made between biomarkers and bioindicators because they can be used in quite different ways and for different purposes in a risk assessment context. As mentioned above, a biomarker is considered to be a surrogate marker of exposure or an early biological marker of effect (e.g., mutations in reporter genes, total chromosome alterations). In contrast, a biological marker of effect that is itself a key event along the pathway from a normal cell to a transformed one is described as a bioindicator (e.g., mutation in critical gene for cancer, cancer-specific chromosome translocation). Biomarkers can be used to inform the dose-response for tumors in a qualitative manner. Bioindicators can be used in a qualitative and quantitative way to inform tnmor dose-response curves. Use of these biomarkers and bioindicators can make it feasible to characterize a dose-response curve at exposure levels below those at which increases in tnmor frequency can be assessed. 

A notable exception to that statement is represented by clear cell sarcoma of soft tissue ( melanoma of soft parts ), which clearly does exhibit true melanocytic dif-ferentiation.2° 2° Because the immunohistologic profiles of that tumor and MM are superimposable, other specialized studies are usually necessary to separate them in cases where clinical findings make the diagnosis uncertain. In particular, clear cell sarcoma regularly shows the presence of a t(12 22) chromosomal translocation, apposing the EWS and ATFl genes, which is not present in melanomas. 

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