Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA
Autor: | Reza Rahbar, Matthew L. Warman, Kyle C. Kurek, Joseph Upton, Kristy L. Rialon, Rashed Rab, David Zurakowski, Wibke Uller, John B. Mulliken, Samantha A. Spencer, Nolan Kamitaki, Steven A. McCarroll, Arin K. Greene, James T. Bennett, Judith V.M.G. Bovée, Andrew L Kirsh, Rudy Murillo, Matthew P. Vivero, Cameron C. Trenor, Harry P.W. Kozakewich, William B. Dobyns, Jonathan A. Perkins, Ahmad I. Alomari, Valerie L. Luks, Steven J. Fishman, Carlos J. Guevara, Reid A. Maclellan |
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Rok vydání: | 2014 |
Předmět: |
Male
Pathology medicine.medical_specialty Klippel-Trenaunay-Weber Syndrome Klippel-Trenaunay syndrome Somatic cell Class I Phosphatidylinositol 3-Kinases Vascular Malformations medicine.disease_cause Polymerase Chain Reaction Article Vascular anomaly Phosphatidylinositol 3-Kinases medicine Humans Abnormalities Multiple Child neoplasms Exome sequencing Mutation Lymphatic Abnormalities business.industry High-Throughput Nucleotide Sequencing Infant DNA medicine.disease Lymphatic system Child Preschool Pediatrics Perinatology and Child Health Female business Fibro-adipose vascular anomaly |
Zdroj: | Journal of Pediatrics, 166(4), 1048-U376 |
ISSN: | 1097-6833 |
Popis: | Objectives To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha ( PIK3CA ) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). Study design We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. Results Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. Conclusions Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low. |
Databáze: | OpenAIRE |
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