Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA.

Marjorie J Lindhurst; Victoria ER Parker; Felicity Payne; Julie C Sapp; Simon Rudge; Julie Harris; Alison M Witkowski; Qifeng Zhang; Matthijs P Groeneveld; Carol E Scott; Allan Daly; Susan M Huson; Laura L Tosi; Michael L Cunningham; Thomas N Darling; Joseph Geer; Zoran Gucev; V Reid Sutton; Christos Tziotzios; Adrian K Dixon; Timothy Helliwell; Stephen O'Rahilly; David B Savage; Michael JO Wakelam; Inês Barroso; Leslie G Biesecker; Robert K Semple

Journal article

Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA.

Marjorie J Lindhurst, Victoria ER Parker, Felicity Payne, Julie C Sapp, Simon Rudge, Julie Harris, Alison M Witkowski, Qifeng Zhang, Matthijs P Groeneveld, Carol E Scott, Allan Daly, Susan M Huson, Laura L Tosi, Michael L Cunningham, Thomas N Darling, Joseph Geer, Zoran Gucev, V Reid Sutton, Christos Tziotzios, Adrian K Dixon Show all

Nature Genetics | Published : 2012

DOI: 10.1038/ng.2332

Abstract

The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in t..

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