New findings may help to clarify why some people contract peritoneal mesothelioma even though they do not appear to have any known risk factors.
Researchers at Boston’s Brigham and Women’s Hospital and Harvard Medical School have identified a genetic abnormality never before linked to malignant mesothelioma. The discovery may not only help clarify these mesothelioma cases, but may also open the door for potential new ways to treat them.
The ALK Gene and Mesothelioma
The gene at the center of the new discovery is anaplastic lymphoma kinase (ALK), a gene responsible for making a protein called ALK receptor tyrosine kinase. ALK receptor tyrosine kinase is believed to play a role in the development of the brain and nervous system.
But ALK has also been linked to the development of cancer. Previous studies suggest that rearrangements in the gene may be behind as many as 60% of cases of a particular variety of non-Hodgkin lymphoma and 3 to 5% of non-small-cell lung cancers.
Gene Rearrangements in Subset of Patient
The new study published this week in the Journal of the American Medical Association is the first to link the ALK gene to peritoneal mesothelioma.
The study included 88 consecutive peritoneal mesothelioma patients treated at Brigham & Women’s between 2005 and 2015. The median age of study subjects was 61, although the youngest patient studied was just 17 years ancient.
The researchers found that approximately 3 percent of the study subjects had a rearrangement in their ALK gene. But that 3 percent was comprised of a very unusual subset of peritoneal mesothelioma patients – a group who fell well outside the “typical” mesothelioma patient profile.
“We identified ALK rearrangements in 3% of cases that (1) present in young women (25% of women younger than 40 years), (2) lack asbestos fibers, (3) have no history of therapeutic radiation, and (4) lack the typical cytogenetic and molecular abnormalities usually present in peritoneal mesothelioma,” states the report.
Asbestos is the primary cause of nearly all cases of malignant mesothelioma, although a small number can come from having had external beam radiation earlier in life. In addition, most mesothelioma cases occur in men over 70.
Why the Findings Matter
The largest challenge in treating an aggressive cancer like malignant mesothelioma is figuring out how to do it without harming healthy cells. The most promising way to minimize side effects and maximize benefits is to develop treatments that single out or “target” mesothelioma cells specifically.
The authors of the new study say the discovery of the link between ALK and peritoneal mesothelioma may offer scientists a “novel pathogenic mechanism” for developing new, highly-targeted mesothelioma therapies to help this unusual group of patients.
No ALK rearrangement was found in patients with pleural mesothelioma.
Hung, Yin, et al, “Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma”, September 14, 2017, JAMA Oncology
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