al published an article in the Journal Genetics in Medicine and we got
permission from the author to share a link on our website.
Kaposiform lymphangiomatosis (KLA) is a rare, frequently aggressive systemic disorder of the lymphatic vasculature, occurring primarily in children. Even with multimodal treatments, KLA has a poor prognosis and high mortality rate secondary to coagulopathy, effusions and systemic involvement. They hypothesized that, as has recently been found for other vascular anomalies, KLA may be caused by somatic mosaic variants affecting vascular development.
al performed exome sequencing of tumor samples from five individuals with KLA,
along with samples from uninvolved control tissue in three of the five. They
used digital polymerase chain reaction (dPCR) to validate the exome findings
and to screen KLA samples from six other individuals.
al identified a somatic activating NRAS variant (c.182A>G, p.Q61R) in
lesional tissue from 10/11 individuals, at levels ranging from 1% to 28%, that
was absent from the tested control tissues.
activating NRAS p.Q61R variant is a known “hotspot” variant, frequently
identified in several types of human cancer, especially melanoma. KLA, therefore,
joins a growing group of vascular malformations and tumors caused by somatic
activating variants in the RAS/PI3K/mTOR signaling pathways. This discovery
will expand treatment options for these high-risk patients as there is potential
for use of targeted NRAS pathway inhibitors.
Read the full publication here.