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Various Chromosomes:
1p, 3p, 6p & q, 8p, 10q, 12q, 13q, 18p, 21q, 22q
A roadmap to future discoveries. The allelotype showed us a large number of chromosomal sites that are
deleted in pancreatic cancer. Some of these are known to have mutant genes.
For example, the deletions of 17p (the short arm of chromosome 17) help to inactivate the
p53 and MKK4 genes that reside there. The p16 gene is on 9p, the DPC4 gene on
18q. But there are other chromosomal arms which are not deleted quite so
universally, but for which losses have been seen in 40-60% of pancreatic cancers. These
sites are listed above, and are also suspected of harboring tumor-suppressor genes.
Because of the large number of these sites, it is likely that they play an important role
in determining the tumor's aggressive behavior. Some are described in more detail:
1p A
region of the short arm of chromosome 1 is lost in nearly 50% of the cancers. The p18
gene, which encodes a cyclin-dependent kinase inhibitor highly similar to p16, is located
in this region of 1p, but is not mutated in the cancers; thus, the tumor-suppressor gene
on 1p remains unknown.
8p A
region of the short arm of chromosome 8 is lost in nearly 50% of the cancers. In one
region of this chromosome, a cell line is known that has deletions of both copies, but it
is not yet clear that there is a tumor-suppressor gene located there.
18p
The losses of 18p probably occur because of the loss of an entire copy of chromosome 18,
including both the short (p) and long (q) arms. Since the laboratory has identified a
major tumor-suppressor gene (DPC4) on the q arm, they view the loss of the p arm as a
"passenger mutation", innocently carried along by the losses which inactivate
one or more genes on 18q.
Both copies of the DCC gene is deleted in a few pancreatic cancers, but DCC is a such a
large gene that it is difficult to study.
22q A
tumor-suppressor gene termed Schwannomin (SCH) is located on chromosome 22q, and is
mutated in neurofibromatosis type 2. They found no mutations of SCH in pancreatic cancer.
Again, another tumor-suppressor gene probably lies on the chromosome and is waiting to be
discovered. |
