(HealthDay)—Many sufferers with arteriovenous malformations of the brain have somatic activating KRAS mutations, in accordance to a research revealed on-line Jan. three within the New England Journal of Medicine.
Sergey I. Nikolaev, Ph.D., from the University of Geneva Medical School, and colleagues examined tissue and blood samples from sufferers with arteriovenous malformations of the brain to detect somatic mutations. Exome DNA sequencing of tissue samples of arteriovenous malformations of the brain was carried out for 26 sufferers in the primary research group and for paired blood samples from 17 of those sufferers. The findings have been confirmed utilizing droplet digital polymerase-chain-reaction evaluation of tissue samples from 39 sufferers in the primary research group (21 with matching blood samples) and from 33 sufferers in an unbiased validation group.
The researchers recognized somatic activating KRAS mutations in tissue samples from 45 of the 72 patients; mutations weren’t recognized in any of the 21 paired blood samples. KRAS mutations have been detected in endothelial cell-enriched cultures derived from arteriovenous malformations of the brain; expression of mutant KRAS in endothelial cells in vitro induced elevated extracellular signal-regulated kinase (ERK) exercise, elevated expression of genes associated to angiogenesis and Notch signaling, and enhanced migratory conduct. Inhibition of mitogen-activated protein kinase-ERK signaling resulted in reversal of those processes.
“We recognized activating KRAS mutations within the majority of tissue samples of arteriovenous malformations of the brain that we analyzed,” the authors write.
One writer disclosed monetary ties to the pharmaceutical business.
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