Functionalized mutation

On pharmacodynamic grounds, tumor resistance may be caused by such diverse mechanisms as the mutation or redundancy of topo II, the overexpression and preferred nuclear localization of proteasome a-type subunits (leading to a anomalous degradation of topo II), genetic deletion or loss-of-function mutations of p53, overexpression of ROS-detoxifying enzymes, overexpression of Bcl-2 (leading to a diminished cyt c release), etc. However, none of these factors would universally predict the development of anthracycline-resistance in a given tumor or another. 

Btk (Bruton s tyrosine kinase) is a phosphatidylinositol 3 -kinase sensitive cytoplasmic tyrosine kinase. Germline loss of function mutations of Btk cause X-linked agammaglobulinaemia in human and X-linked immunodeficiency in mice. 

Nickel RG, Casolaro V, Wahn U, et al. Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES. J Immunol 2000 164(3) 1612-1616. 

Herrera, G., Urios, A., Alexandre, V, and Blanco, M., (1988). UV light induced mutability in Salmonella strains containing the limit DC or the mite AB operon evidence for a limit C function. Mutation Res. 198 9-13. 

Los s-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation, 115, 442-449. 

Blanpain, C., Le Poul, E., Parma, J., Knoop, C., Detheux, M., Parmentier, M., Vassart, G. and Abramowicz, M.J. (2003) Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine-associated primary pulmonary hypertension. Cardiovascular Research, 60 (3), 518-528. 

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