Breast Cancer
In 4 breast tumors (114480) from a series of 284 primary human tumors, Campbell et al. (2004) identified a 1340A-T transversion in exon 20 of the PIK3CA gene, resulting in a his1047-to-leu (H1047L) substitution.
CLOVE Syndrome
Lindhurst et al. (2012) 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 H1047L mutation in the PIK3CA gene in affected cells only, the p110-catalytic subunit of PI3K, only in affected cells, with a mutation burden determined to be from 8% to 39%. The same H1047L alteration was identified in 2 of 9 other individuals with the 'unclassified' syndrome, with mutation burdens ranging from 4% to 49%. The features of the syndrome were consistent with CLOVE syndrome (612918).
CLAPO Syndrome
In tissue from a lymphatic malformation (LM) of the tongue of a 7-year-old female patient (P13) with CLAPO syndrome (613089), Rodriguez-Laguna et al. (2018) identified a c.3140A-T transversion (c.3140A-T, NM_006218.2) in the PIK3CA gene that resulted in a his1047-to-leu (H1047L) mutation in the kinase domain. The mutation was present at an allele frequency of 16% by deep sequencing, was present in 315 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and had been previously reported in 30 patients with vascular overgrowth disorders. Functional studies were not performed.
Cerebral Cavernous Malformations 4
In samples of cerebral cavernous malformations-4 (CCM4; 619538) from 2 unrelated patients with sporadic occurrence of the disease, Peyre et al. (2021) identified a somatic H1047L mutation in the PIK3CA gene. The mutation was found by targeted DNA sequencing. PIK3CA-mutant CCMs showed increased phosphorylation of myosin light chain and activation of the PI3K-AKT-mTOR pathway, consistent with an activating mutation.
