Cancer


Figure 15-11 The Philadelphia chromosome translocation, t(9;22)(q34;q11). The Philadelphia chromosome (Ph1) is the derivative chromosome 22, which has exchanged part of its long arm for a segment of material from chromosome 9q that contains the ABL1 oncogene. Formation of the chimeric BCRABL1 gene on the Ph1 chromosome is the critical genetic event in the development of chronic myelogenous leukemia.


In other cases, a translocation activates an oncogene by placing it downstream of a strong, constitutive promoter belonging to a different gene. Burkitt lymphoma is a B-cell tumor in which the MYC proto-oncogene is translocated from its normal chromosomal position at 8q24 to a position distal to the immunoglobulin heavy chain locus at 14q32 or the immunoglobulin light chain genes on chromosomes 22 and 2. The function of the Myc protein is still not entirely known, but it appears to be a transcription factor with powerful effects on the expression of a number of genes involved in cellular proliferation, as well as on telomerase expression (see later discussion). The translocation brings enhancer or other transcriptional activating sequences, normally associated with the immunoglobulin genes, near to the MYC gene (Table 15-4). These translocations allow unregulated MYC expression, resulting in uncontrolled cell division.



TABLE 15-4


Characteristic Chromosome Translocations in Selected Human Malignant Neoplasms


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Based on Croce CM: Role of chromosome translocations in human neoplasia, Cell 49:155-156, 1987; Park M, van de Woude GF: Oncogenes: genes associated with neoplastic disease. In Scriver CR, Beaudet AL, Sly WS, Valle D, editors: The molecular and metabolic bases of inherited disease, ed 6, New York, 1989, McGraw-Hill, pp 251-276; Nourse J, Mellentin JD, Galili N, et al: Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor, Cell 60:535-545, 1990; and Borrow J, Goddard AD, Sheer D, Solomon E: Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17, Science 249:1577-1580, 1990.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Cancer

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