Causal somatic mutations in urine DNA from persons with the CLOVES subgroup of the PIK3CA Related Overgrowth Spectrum (PROS).

Causal somatic mutations in urine DNA from persons with the CLOVES subgroup of the PIK3CA Related Overgrowth Spectrum (PROS). Clin Genet. 2017 Dec 12;: Authors: Michel ME, Konczyk DJ, Yeung KS, Murillo R, Vivero MP, Hall AM, Zurakowski D, Adams D, Gupta A, Huang AY, Chung BHY, Warman ML Abstract Congenital Lipomatous Overgrowth with Vascular, Epidermal, and Skeletal anomalies (CLOVES) and Klippel-Trenaunay (KTS) syndromes are caused by somatic gain-of-function mutations in PIK3CA, encoding a catalytic subunit of phosphoinositide 3-kinase. Affected tissue is needed to find mutations, since mutant alleles are not detectable in blood. Because some patients with CLOVES develop Wilms tumor, we tested urine as a source of DNA for mutation detection. We extracted DNA from the urine of 17 and 24 individuals with CLOVES and KTS, respectively, and screened 5 common PIK3CA mutation hotspots using droplet digital PCR. Six of 17 CLOVES participants (35%) had mutant PIK3CA alleles in urine. Among 8 individuals in whom a mutation had been previously identified in affected tissue, 4 had the same mutant allele in the urine. One study participant with CLOVES had been treated for Wilms tumor. We detected the same PIK3CA mutation in her affected tissue, urine, and tumor, indicating Wilms tumors likely arise from PIK3CA mutant cells in patients with CLOVES. No urine sample from a participant with KTS had detectable PIK3CA mutations. We suggest that urine...
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research