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  • A somatic activating NRAS variant associated with kaposiform lymphangiomatosis GENETICS IN MEDICINE Barclay, S. F., Inman, K. W., Luks, V. L., McIntyre, J. B., Al-Ibraheemi, A., Church, A. J., Perez-Atayde, A. R., Mangray, S., Jeng, M., Kreimer, S. R., Walker, L., Fishman, S. J., Alomari, A. I., Chaudry, G., Trenor, C. C., Adams, D., Kozakewich, H. W., Kurek, K. C. 2019; 21 (7): 1517–24
  • A somatic activating NRAS variant associated with kaposiform lymphangiomatosis. Genetics in medicine : official journal of the American College of Medical Genetics Barclay, S. F., Inman, K. W., Luks, V. L., McIntyre, J. B., Al-Ibraheemi, A., Church, A. J., Perez-Atayde, A. R., Mangray, S., Jeng, M., Kreimer, S. R., Walker, L., Fishman, S. J., Alomari, A. I., Chaudry, G., Trenor Iii, C. C., Adams, D., Kozakewich, H. P., Kurek, K. C. 2018

    Abstract

    PURPOSE: 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. We hypothesized that, as has recently been found for other vascular anomalies, KLA may be caused by somatic mosaic variants affecting vascular development.METHODS: We performed exome sequencing of tumor samples from five individuals with KLA, along with samples from uninvolved control tissue in three of the five. We used digital polymerase chain reaction (dPCR) to validate the exome findings and to screen KLA samples from six other individuals.RESULTS: We identified a somatic activating NRAS variant (c.182 A>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.CONCLUSION: The 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 RAS pathway inhibitors.

    View details for PubMedID 30542204

  • HDAC INHIBITION IN THALAMIC AND SPINAL CORD H3K27M+DIFFUSE MIDLINE GLIOMA Kreimer, S., Lin, G., Woo, P., Monje-Deisseroth, M. OXFORD UNIV PRESS INC. 2018: 50
  • ANTICOAGULATION FOR TREATMENT OF PAIN IN VENOUS MALFORMATIONS Chien, M., Kreimer, S., Teng, J., Marqueling, A., Jeng, M. WILEY. 2018
  • HDAC INHIBITION IN THALAMIC AND SPINAL CORD H3K27M+DIFFUSE MIDLINE GLIOMA Kreimer, S., Woo, P., Monje-Deisseroth, M. WILEY. 2018