Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25681199
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Lymphatic and other vascular malformative/overgrowth disorders are caused by
somatic mutations in PIK3CA
#MMPMID25681199
Luks VL
; Kamitaki N
; Vivero MP
; Uller W
; Rab R
; Bovée JV
; Rialon KL
; Guevara CJ
; Alomari AI
; Greene AK
; Fishman SJ
; Kozakewich HP
; Maclellan RA
; Mulliken JB
; Rahbar R
; Spencer SA
; Trenor CC 3rd
; Upton J
; Zurakowski D
; Perkins JA
; Kirsh A
; Bennett JT
; Dobyns WB
; Kurek KC
; Warman ML
; McCarroll SA
; Murillo R
J Pediatr
2015[Apr]; 166
(4
): 1048-54.e1-5
PMID25681199
show ga
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.
free
free
free
