“PIK3CA-related overgrowth spectrum”的意思、由来-开放百科全书

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term for rare syndromes characterized by malformations and tissue overgrowth caused by somatic mutations in PIK3CA gene^[1]^[2]^[3]. In PROS diseases individuals malformations are seen in several different tissues such as skin, vasculature, bones, fat and brain tissue depending on the specific disease.

Pathophysiology

PIK3CA gene codes for p110α protein which is a catalytic subunit of phosphoinositide 3-kinase, a major regulator of several important cellular functions such as cell proliferation, growth and apoptosis.^[4]. Mutations in PIK3CA cause over-activity of PI3K which in turn leads to altered growth of cells and tissues which is thought to be important for overgrowth and malformations in PROS^[5]. Different presentations of PROS diseases are likely explained by acquisition of the mutation in different time points and different cell types during embryonic development ^[5]

Treatment

Treatment of PROS diseases is variable and depends on the specific disease. Curative treatment does not exist and most treatments are given to control symptoms. Overgrowth and malformations of solid tissues can be treated with surgery. Sclerotherapy can be used to treat vascular malformations^[5]. In CLOVES syndrome experimental medical therapy using PIK3CA inhibitor, BYL719, has been reported to be effective to relief pain and diminish the malformations^[6].

References

1. ^{{cite web |url=https://rarediseases.info.nih.gov/diseases/12182/pik3ca-related-overgrowth-spectrum |title=PIK3CA-related overgrowth spectrum |publisher=National Institute of Health |website=rarediseases.info.nih.gov |access-date=2018-10-03 |archive-url=https://web.archive.org/web/20180802164128/https://rarediseases.info.nih.gov/diseases/12182/pik3ca-related-overgrowth-spectrum |archive-date=2018-08-02 |dead-url=no |df= }}
2. ^{{Cite journal|last=Keppler-Noreuil|first=Kim M.|last2=Rios|first2=Jonathan J.|last3=Parker|first3=Victoria E. R.|last4=Semple|first4=Robert K.|last5=Lindhurst|first5=Marjorie J.|last6=Sapp|first6=Julie C.|last7=Alomari|first7=Ahmad|last8=Ezaki|first8=Marybeth|last9=Dobyns|first9=William|date=2014-12-24|title=PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation|journal=American Journal of Medical Genetics. Part A|volume=167A|issue=2|pages=287–295|issn=1552-4833|pmc=4480633|pmid=25557259|doi=10.1002/ajmg.a.36836}}
3. ^{{Cite web|url=http://issva.org/classification|title=Classification {{!}} International Society for the Study of Vascular Anomalies|website=issva.org|access-date=2018-09-23|archive-url=https://web.archive.org/web/20180329100513/http://www.issva.org/classification|archive-date=2018-03-29|dead-url=no|df=}}
4. ^{{Cite journal|last=Fruman|first=David A.|last2=Chiu|first2=Honyin|last3=Hopkins|first3=Benjamin D.|last4=Bagrodia|first4=Shubha|last5=Cantley|first5=Lewis C.|last6=Abraham|first6=Robert T.|date=2017-08-10|title=The PI3K Pathway in Human Disease|journal=Cell|volume=170|issue=4|pages=605–635|doi=10.1016/j.cell.2017.07.029|issn=1097-4172|pmc=5726441|pmid=28802037}}
5. ^¹²{{Cite journal|last=Madsen|first=Ralitsa R.|last2=Vanhaesebroeck|first2=Bart|last3=Semple|first3=Robert K.|date=2018-09-06|title=Cancer-Associated PIK3CA Mutations in Overgrowth Disorders|journal=Trends in Molecular Medicine|volume=24|issue=10|pages=856–870|doi=10.1016/j.molmed.2018.08.003|issn=1471-499X|pmid=30197175}}
6. ^{{Cite journal|last=Venot|first=Quitterie|last2=Blanc|first2=Thomas|last3=Rabia|first3=Smail Hadj|last4=Berteloot|first4=Laureline|last5=Ladraa|first5=Sophia|last6=Duong|first6=Jean-Paul|last7=Blanc|first7=Estelle|last8=Johnson|first8=Simon C.|last9=Hoguin|first9=Clément|date=2018-06-13|title=Targeted therapy in patients with PIK3CA-related overgrowth syndrome|journal=Nature|volume=558|issue=7711|pages=540–546|issn=1476-4687|pmid=29899452|doi=10.1038/s41586-018-0217-9}}