Gene study turns up 26 lung cancer genes

By Julie Steenhuysen

CHICAGO (Reuters) - A broad analysis of genes has turned up 26 mutations linked with the most common form of lung cancer, several of which play a role in other cancers as well, researchers said on Wednesday.

The findings, published in the journal Nature, double the number of genes already linked with lung adenocarcinoma, a type of non-small cell lung cancer that accounts for 40 percent of the more than 1 million lung cancer deaths each year.

"We think that our study may achieve a real impact on the cure of lung cancer patients," Dr. Matthew Meyerson of the Broad Institute of Massachusetts Institute of Technology and Harvard University said in a telephone briefing.

Meyerson was part of an international team that decoded 623 genes from tumors in 188 lung cancer patients and compared these to genes from normal tissues from the same people.

They found 26 genes that were most commonly altered in the tumors, most of which had never been linked with lung cancer. Some had been found in other types of tumors.

The new genes included mutations in neurofibromatosis 1, a gene known to cause a rare neurological disorder and raise the risk of nerve and brain tumors; ataxia telengiectasia mutated or ATM, which has ties with leukemia and lymphoma; retinoblastoma 1, which is linked with a rare childhood cancer of the eye; and adenomatosis polyposis coli or APC, which is common in colon cancer.

Many of the mutated genes also share common biological pathways or gene networks.

"Looking at the pathways helps simplify the picture," said Richard Wilson of Washington University in St. Louis, who helped lead the project.

PROMISING DRUGS

One of the most promising of these pathways is the mitogen-activated protein kinase or MAPK pathway, altered in more than 70 percent of the tumors. Drug compounds called MEK inhibitors that affect this pathway have already shown promise in mice with lung cancer.

About half of the tumors had defects in the p53 pathway, which is critical for suppressing tumor growth. Companies such as Introgen Therapeutics Inc are working on drugs that affect this pathway.

Some 30 percent of the tumors had mutations in the mTOR pathway, raising hope that drugs that inhibit the mTOR protein might help some lung cancer patients. Swiss drugmaker Novartis' mTOR inhibitor for kidney cancer, Afinitor, is currently under review by U.S. regulators.

The researchers also saw that a familiar class of genes known as tyrosine kinases, which trigger cell growth, played a key role in lung tumors. Gene families in this group include EGFR and VEGF.

Genentech and Roche Holding AG's drug Avastin targets VEGF, while their pill for advanced lung cancer called Tarceva interferes with EGFR. A recent study found combining the two did little to help lung cancer patients live any longer.

Meyerson said genetic testing may help determine which patients might benefit from current drugs, but he said many new drugs will likely come from the findings as well.