Chromosome Organization within the Nucleus
11
to a translocation called the Philadelphia
chromosome, and the breakpoint encodes
a novel fusion protein called BCR-ABL.
The majority of patients with chronic
myelogenous leukemia (CML) contain this
rearrangement in their genomes. Why is
this rearrangement so common? FISH
measurements show that BCR and ABL
loci are in fact nonrandomly close together
in the nucleus, which may account for the
high frequency of recombination between
these two loci. Another rearrangement im-
portant for cancer involves the RET and
H4 loci. An inversion with breakpoints in
RET and H4 is found in many cases of
radiation-induced thyroid cancer. As with
BCR and ABL, RET and H4 are nonran-
domly close together in normal cells, again
suggesting that it is the spatial proximity
of these loci that allows them to recombine
so frequently.
7
Conclusions
Clearly, a more detailed understanding
of nuclear architecture is critical for the
progress of molecular medicine. Under-
standing how the speci±c positioning of
genes occurs, and what influence this
positioning has on gene expression and
recombination, will lead to a clearer un-
derstanding of chromosome behavior in
interphase. The key is to uncover the
molecular players that establish and main-
tain nuclear architecture.
Acknowledgments
Wallace F. Marshall was funded by a
Leukemia and Lymphoma Society Spe-
cial Fellowship.
See also
Cell Nucleus Biogenesis,
Structure and Function; Electron
Microscopy in Cell Biology.
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