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Leukaemia Research
Positional cloning : from chromosomes to chimaeric genes in human leukaemia
The molecular dissection of structural chromosome alterations found
in cancer cells has identified more than 100 cancer-related genes. Aside
from their diagnostic and prognostic value, this genetic information
is providing new information that is critical to our current understanding
of the molecular pathways of cancer development and progression. A better
understanding of these pathways is a necessary precedent to the design
of more effective treatments.
Structural chromosome rearrangements contribute to malignant transformation
by one of two main mechanisms - either by the deregulation of a cellular
gene, or by creating a transforming fusion gene. In the latter case,
the genes at the breakpoint junctions of chromosome translocation are
often transcription factors, and normally involved in developmental processes
of cell differentiation. We are studying a novel t(5;10)(q22;q24) associated
with acute lymphoblastic leukaemia (ALL), and our research to date has
identified a single large-insert genomic clone that contains the 10q24
breakpoint. Our current investigations aim to identify the site of breakage
within this clone, and to identify and characterise genes that span or
map close to its vicinity.
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