cancer is notoriously difficult to detect in its early
stages because there are frequently few symptoms and current
imaging techniques are not specific for cancer.
Vogelstein, M.D., professor and director of the Ludwig
Center for Cancer Genetics and Therapeutics at the Johns
Hopkins Kimmel Cancer Center and an investigator at the
Howard Hughes Medical Institute, says the results show
that "many pancreatic cancer cases have a long lag time
before they are detected through conventional tests. This
leaves room to develop new early, diagnostic tools and
intervene with potentially curative surgery."
Johns Hopkins work, published in the Oct. 28 issue of
the journal Nature, suggests that it takes at least a
decade for the first cancer-causing mutation that occurs
in a cell in a pancreatic lesion to turn into a full-fledged
cancer cell. At this point, the lesion is called "high-grade"
and should be removed, much like polyps are removed from
the first cancer cell appears, it takes an average of
nearly seven years for that cell to turn into the billions
that make up a cancerous tumor the size of a plum, after
which at least one of the cells within the tumor has the
potential and ability to spread to other organs. Patients
die an average of two and a half years after this metastasis.
results contradict the idea that pancreatic cancers metastasize
very early in their development, says Iacobuzio-Donahue.
the study, scientists collected tissue samples during
autopsies of seven patients who died from pancreatic cancer
that had metastasized to other organs. Because the tissue
samples were taken within six hours of each patient's
death, the scientists were able to keep some of the cells
alive long enough to extract the DNA and sequence the
series of chemical "letters" that form genes.
all patients, metastatic deposits were found in two or
more sites in the body, most often the liver, lung and
peritoneum (lining of the abdomen). The researchers found
similar mutations present in both the areas of metastasis
and in the primary pancreatic tumors from which the metastases
also identified and classified the types of mutations
- ones that occur before metastasis and others that happen
after the cancer has spread. Both types of mutations were
present within the primary tumor years before the metastases
became clinically evident, according to Iacobuzio-Donahue.
mathematical models to study the timing of pancreatic
cancer progression, the scientists conservatively estimated
an average of 11.7 years before the first cancer cell
develops within a high-grade pancreatic lesion, then an
average of 6.8 years as the cancer grows and at least
one cell has the potential to spread, and finally, an
average of 2.7 years from then until a patient's death.
Johns Hopkins scientists say the goal is develop a pancreatic
cancer screening method similar to the protocol used for
breast and colon cancer. Though early stages of pancreatic
cancer cause no symptoms, Iacobuzio-Donahue says, perhaps
at a certain age people should undergo an endoscopy to
screen for pancreatic cancer. Endoscopy is a procedure
allowing doctors to look inside the body through the use
of an instrument that has a tiny camera attached to a
long, thin tube.
study published in the same issue of Nature, directed
by British researchers at the Wellcome Trust Sanger Institute
in collaboration with Iacobuzio-Donahue, used cell lines
and tissue samples from the same pancreatic cancer patients
as the Johns Hopkins study to look for rearrangements
of genetic material. They found more than half of specific
rearrangements occurred in all metastases and primary
genome sequencing work was supported by the National Institutes
of Health, the Bill and Melinda Gates Foundation, the
Uehara Memorial Foundation, the AACR-Barletta Foundation,
the John Templeton Foundation, the Sol Goldman Pancreatic
Cancer Research Center, the Michael Rolfe Pancreatic Cancer
Foundation, the George Rubis Endowment for Pancreatic
Cancer Research, the Joseph C. Monastra Foundation for
Pancreatic Cancer Research, the Alfredo Scatena Memorial
Fund, Sigma Beta Sorority, the Skip Viragh Foundation,
the Virginia and the D.K. Ludwig Fund for Cancer Research,
the Joint Program in Mathematical Biology and J. Epstein.
scientists involved in the research were Shinichi Yachida,
Siân Jones, Rebecca Leary, Baojin Fu, Mihoko Kamiyama,
Ralph H. Hruban, James R. Eshleman, Victor E. Velculescu,
and Kenneth W. Kinzler of Johns Hopkins; Ivana Bozic and
Martin A. Nowak of Harvard University in Cambridge,
Johns Hopkins Medical Institutions