Lung cancers involve many different genetic mutations

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Twenty-six different genes are frequently mutated in the most common form of lung cancer, lung adenocarcinoma, according to a study published in the journal Nature. That more than doubles in one swoop the number of genes known to be implicated in this cancer.

We’re not talking about genes that were mutated from birth in individuals -- rather, genetic mistakes that accumulated in lung tissue throughout individuals’ lifetimes. To track these genes down, the researchers (who are members of the Tumor Sequencing Project, which is a consortium of scientists from several universities) compared samples of lung cancer tissue to non-cancerous tissue donated by 188 patients with lung adenocarcinoma, screening for genetic mistakes in 623 genes that were already known to be linked to other types of cancers.

Among the 26 genes they found were Retinoblastoma 1, linked to a childhood eye cancer; Neurofibromatosis 1, linked to a rare genetic disorder of uncontrolled nerve tissue; another with a mouthful of a name -- Ataxia Telengiectasia Mutated -- linked to some leukemias and lymphoma as well as a rare neurological childhood disorder.

The findings should be medically useful, researchers say, because the 26 genes are known to be involved in a variety of biological pathways through which cells get their housekeeping done. Sometimes, in cancers, these pathways get turned on when they should be off, or ramped up too high, or too low. If scientists know that a pathway’s gone awry in a cancer cell, they can use a drug to interfere with that pathway -- and by so doing, maybe block the growth of a tumor.

The researchers found, for example, that two-thirds of the tumors had an altered ‘MAPK’ pathway -- and there are drugs already known to act against that pathway, called MEK inhibitors. Thus they may prove promising in lung cancer treatment. (MEK inhibitors have been tested with some success in mice with colon cancer, though we all know to be wary about making too much of mouse cures.)

The researchers also found key differences between cancers in people with significant histories of smoking, and those who hadn’t smoked but still got lung cancer. Smokers’ cancers contained many more genetic mutations -- as many as 49, compared with just five in the tumors of nonsmokers.

The degree of genetic variation in the sample is no surprise. Cancer, scientists are learning, is not just one disease -- different genetic mutations can turn a cell rogue. That undestanding is fueling the conviction that cancers, ideally, should be treated in a personalized way -- because the drug that works for one group of patients may not work well for another. Check out the article by Shari Roan on that topic in this week’s Health section (a special on cancer).

-- Rosie Mestel