Genes map study finds clues to pancreatic cancer

Last Updated: Sunday, January 23, 2011 - 00:00

Washington: Experts in the genetics of cancer said on Thursday they have found out why some people can live for years with the same kind of rare pancreatic cancer that affects Apple CEO Steve Jobs.

They identified new genes that, when mutated in a certain way, appear to cause a relatively less harmful form of pancreatic neuroendocrine tumor.

Patients with these mutations lived twice as long as those whose tumors carried other mutations, the team at Johns Hopkins University in Baltimore report in the journal Science.

"This is the new molecular view of cancer. The genetic makeup of the cancer will determine what the management (for) this person would be," Nickolas Papadopoulos, one of the researchers who led the study, said in a telephone interview.

Pancreatic cancer is one of the deadliest cancers, killing 95 percent of patients within five years.

But doctors realize that identifying cancer by the organ where it starts in only a very crude tool. Tumors vary in their aggressiveness and makeup, and studies show that particular genetic mutations may be more useful for deciding how to treat a patient and predicting how well he or she will do.

Pancreatic cancer is diagnosed in nearly 37,000 people a year in the United States and kills more than 34,000, according to the American Cancer Society.

But most of these cases are a type of tumor called adenocarcinoma. Neuroendocrine tumors, which account for about 5 percent of pancreatic cancer cases, are more easily treated and less aggressive. About 40 percent of patients are still alive 10 years later.

Baffling case

Jobs has baffled experts and shareholders. He said in 2004 he had undergone successful surgery for a pancreatic islet cell neuroendocrine tumor but gave no details.

He had a liver transplant in 2009, which could be a treatment for tumor spread, and just announced on Monday he would go on medical leave again but did not say why.

Papadopoulos and colleagues on Hopkins cancer expert Dr. Bert Vogelstein`s team sequenced all the DNA taken from tumors of 68 patients with pancreatic neuroendocrine tumors.

Patients whose tumors had mutations in three genes called MEN-1, DAXX and ATRX had lived at least 10 years after diagnosis, they reported in Science.

More than 60 percent of patients whose tumors did not have these mutations died within five years, they found.

MEN-1 was common, seen in more than 44 percent of the 68 patients.

"That indicates that mutations in these genes is a good prognostic marker for these individuals," Papadopoulos said.

"What this tells us is that it may be more useful to classify cancers by gene type rather than only by organ or cell type."

The researchers only looked at a subset of pancreatic neuroendocrine tumors -- the silent type that do not cause obvious hormonal symptoms such as weight gain and skin rashes, so their findings do not give much information about the other types.

The researchers found some other potentially good news for patients. Fourteen percent of the tumors carried mutations in a gene family called mTOR.

There are already drugs on the market that affect mTOR genes, including rapamycin, also known as sirolimus, and a similar drug called temsirolimus. Rapamycin is sold under the brand name Rapamune by Pfizer Inc. and is prescribed to suppress the immune system in transplant patients.

Bureau Report



First Published: Sunday, January 23, 2011 - 00:00

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