Genetic rearrangement in the ALK gene found in young women with mesothelioma may be targetable with FDA-approved drugs — ScienceDaily

Mesothelioma is a rare and aggressive tumor that, in many cases, results from exposure to asbestos. But over the last several decades, other causes of the disease have emerged, including treatment with high-intensity therapeutic radiation and, more recently, an inherited genetic mutation. Now, through an unexpected observation and a meticulous study of patients seen at Brigham and Women’s Hospital, BWH investigators have added a fourth cause to the list: a genetic rearrangement in the ALK gene, observed in three patients with peritoneal mesothelioma. Unlike previously known causes, this new discovery points to a potential therapeutic approach for those few patients whose tumors harbor the mutation.

The team’s findings are published in JAMA Oncology.

“Mesothelioma is highly lethal and has no cure. Often, it is not diagnosed until at a late stage, when many tumors have already formed,” said principal investigator Lucian Chirieac, MD, a thoracic oncology pathologist in the Department of Pathology at BWH and associate professor at Harvard Medical School. “Although this mutation only exists in a small percentage of cases, this discovery points to a potential therapeutic avenue for these patients.”

There are about 3,000 new cases of mesothelioma each year in the U.S., and only about 300 of those are peritoneal mesothelioma, which forms in the lining of the abdomen. Most cases of mesothelioma result decades after exposure to asbestos or radiation therapy. But in rare cases, young patients who have never been exposed to either risk factor are diagnosed with the disease. One such case led Chirieac and his colleagues to their unexpected finding.

“This was a serendipitous discovery. We had a young patient with peritoneal mesothelioma that was difficult to diagnose. We extended our molecular diagnostics to test for a genetic rearrangement that had been reported in lymphoma and lung cancer, but never in mesothelioma. When it came back positive, we were intrigued,” said first…

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