Chromosomal Translocations

Genetic Control. Manipulation of the mechanisms of inheritance of the insect pest populations has occurred most successhiUy through the mass release of steri1i2ed males, but a variety of other techniques have been studied, including the environmental use of chemostetilants and the mass introduction of deleterious mutations, eg, conditional lethals and chromosomal translocations (58 ndash 60) (see Genetic engineering). 

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. 

Chromosomal Translocations Chromosome Segregation Chromosomes Chronic Bronchitis... 

O A chromosomal translocation, the Philadelphia chromosome, is responsible for chronic myelogenous leukemia (CML). 

Chromosomal translocations have become a hallmark of many lymphomas and are helpful in the diagnosis and classification of lymphoid malignancies. NHL often involves extranodal sites and does not spread through contiguous lymph nodes. 

A well-known use of molecular methods is in the study of chromosomal translocations. Thus, in Philadelphia chromosome (ph1) positive chronic myelogenous leukemia (CML), the C-abl oncogene on chromosome 9 is translocated to a region on chromosome 22 called the breakpoint cluster region, or bcr. This (t9 22) translocation results in production of an abnormal fusion protein... 

Beige, G., B. Kazmierczak, K. Meyer-Bolte, S. Bartnitzke, and J. Bullerdiek. 1992. Expression of SV40 T-antigen in lipoma cells with a chromosomal translocation T(3 12) is not sufficient for direct immortalization. Cell Biol Int Rep 16(4) 339-47. 

Figure 2. Genetic aberrations observed in HAT genes, (a) Schematic representation of a balanced chromosomal translocation. These translocations result in the formation two new fusion genes, which can give rise to one or two fusion proteins, (b) Examples of nonsense (RTS patient RT163.1), missense (RT209.1), deletion (followed by frame shift RT231.1) mutations, as well as sphee site acceptor (RT211.3) or splice site donor (RT39.1) mutations...

Imamura T, Kakam N, Hibi S, Morimoto A, Eukushima Y, ljuin 1, Hada S, Kitabayashi 1, Abe T, Imashuku S (2003) Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2 8)(p23 pll). Genes Chromosomes. Cancer 36 413 19... 

MYST family HATs frequently fused to other proteins as a result of chromosomal translocation in acute myeloid leukemia. 

Figure 2. Chromosomal translocations leading the production of a MYST HAT fusion protein and cancer, (a) structure of different MYST HAT fusion proteins leading to cancer. Numbers indicate amino acid positions at break points, (b) Model for die consequences of EPCl-PCL fusion on chromatin function...

Kitabayashi 1, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M (2001a) Activation of AMLl-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. Embo J 20 7184-7196 Kitabayashi 1, Aikawa Y, Yokoyama A, Hosoda F, Nagai M, Kakazu N, Abe T, Ohki M (2001b) Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8 22)(pll ql3) chromosome translocation. Leukemia 15 89-94... 

Translocations occur when chromosomes are broken and the broken elements reattach to other chromosomes. Translocations can be classified into two major types, reciprocal and Robertsonian. 

Long, A. A., Komminoth, P., Lee, E., and Wolfe, H. J. (1993) Comparison of indirect and direct in situ polymerase chain reaction in cell preparations and tissue sections. Detection of viral DNA gene rearrangements and chromosomal translocations. Histochemistry 99, 151-162. 

Miyamoto, T., Weissman, I. and Akashi, K. (2000) AMLl/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8 21 chromosomal translocation. Proc. Natl. Acad. Scl. USA 97, 7521-7526. 

Mori, H., Colman, S., Xiao, Z., Ford, A., Healy, L., Donaldson, C., Hows, J., Navarrete, C. and Greaves, M. (2002) Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc. Natl. Acad. Scl. USA 99, 8242-8247. 

Enl is a translocation partner for MLL that is a common target for chromosomal translocations in human acute leukemia. Truncating mutations of hSNF5/INH are associated with aggressive pediatric cancer... 

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

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