When, where and which PIK3CA mutations are pathogenic in congenital disorders
Angulo-Urarte, Ana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Graupera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Data:	2022
Resum:	PIK3CA encodes the class I PI3Kα isoform and is frequently mutated in cancer. Activating mutations in PIK3CA also cause a range of congenital disorders featuring asymmetric tissue overgrowth, known as the PIK3CA-related overgrowth spectrum (PROS), with frequent vascular involvement. In PROS, PIK3CA mutations arise postzygotically, during embryonic development, leading to a mosaic body pattern distribution resulting in a variety of phenotypic features. A clear skewed pattern of overgrowth favoring some mesoderm-derived and ectoderm-derived tissues is observed but not understood. Here, we summarize our current knowledge of the determinants of PIK3CA-related pathogenesis in PROS, including intrinsic factors such as cell lineage susceptibility and PIK3CA variant bias, and extrinsic factors, which refers to environmental modifiers. We also include a section on PIK3CA-related vascular malformations given that the vasculature is frequently affected in PROS. Increasing our biological understanding of PIK3CA mutations in PROS will contribute toward unraveling the onset and progression of these conditions and ultimately impact on their treatment. Given that PIK3CA mutations are similar in PROS and cancer, deeper insights into one will also inform about the other. In this Review, the authors provide an overview of the pathogenic effects of somatic activating PIK3CA mutations in congenital disorders and discuss how the interplay between genetics, cell identity and the environment explains the onset, progression and severity of these disorders with a special focus on the vasculature.
Ajuts:	Ministerio de Ciencia e Innovación PID2020-116184RB-110
Nota:	Altres ajuts: PTEN RESEARCH Foundation (BRR-17-001/IJC-21-001); Fundació La Caixa (LCF/PR/PR16/51110035 i LCF/PR/HR19/52160023)
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Llengua:	Anglès
Document:	Article de revisió ; Versió sotmesa a revisió
Matèria:	Diseases ; Genetics
Publicat a:	Nature cardiovascular research, Vol. 1 Núm. 8 (2022) , p. 700-714, ISSN 2731-0590

DOI: 10.1038/s44161-022-00107-8

Preprint 51 p, 2.3 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
Articles > Articles publicats