FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4226145885> ?p ?o ?g. }

• W4226145885 abstract "Abstract Recurrent missense mutations of the PIK3CA oncogene are among the most frequent drivers of human cancers. These often lead to constitutive activation of its product p110α, a phosphatidylinositol 3-kinase (PI3K) catalytic subunit. In addition to causing a broad range of cancers, the H1047R mutation is also found in affected tissues of a distinct set of congenital tumors and malformations. Collectively termed PIK3CA -related disorders (PRDs), these lead to overgrowth of brain, adipose, connective and musculoskeletal tissues and/or blood and lymphatic vessel components. Vascular malformations are frequently observed in PRD, due to cell-autonomous activation of PI3K signaling within endothelial cells. These, like most muscle, connective tissue and bone, are derived from the embryonic mesoderm. However, important organ systems affected in PRDs are neuroectodermal derivatives. To further examine their development, we drove the most common post-zygotic activating mutation of Pik3ca in neural crest and related embryonic lineages. Outcomes included macrocephaly, cleft secondary palate and more subtle skull anomalies. Surprisingly, Pik3ca -mutant subpopulations of neural crest origin were also associated with widespread cephalic vascular anomalies. Mesectodermal neural crest is a major source of non-endothelial connective tissue in the head, but not the body. To examine the response of vascular connective tissues of the body to constitutive Pik3ca activity during development, we expressed the mutation by way of an Egr2 (Krox20) Cre driver. Lineage tracing led us to observe new lineages that had normally once expressed Krox20 and that may be co-opted in pathogenesis, including vascular pericytes and perimysial fibroblasts. Finally, Schwann cell precursors having transcribed either Krox20 or Sox10 and induced to express constitutively active PI3K were associated with vascular and other tumors. These murine phenotypes may aid discovery of new candidate human PRDs affecting craniofacial and vascular smooth muscle development as well as the reciprocal paracrine signaling mechanisms leading to tissue overgrowth." @default.
• W4226145885 created "2022-05-05" @default.
• W4226145885 creator A5019272527 @default.
• W4226145885 creator A5023205638 @default.
• W4226145885 creator A5026570144 @default.
• W4226145885 creator A5033020273 @default.
• W4226145885 creator A5036634814 @default.
• W4226145885 creator A5053687021 @default.
• W4226145885 creator A5061573562 @default.
• W4226145885 creator A5064412163 @default.
• W4226145885 creator A5085631360 @default.
• W4226145885 date "2022-04-06" @default.
• W4226145885 modified "2023-10-09" @default.
• W4226145885 title "Multiple congenital malformations arise from somatic mosaicism for constitutively active Pik3ca signaling" @default.
• W4226145885 cites W1565566882 @default.
• W4226145885 cites W1835943580 @default.
• W4226145885 cites W1854254479 @default.
• W4226145885 cites W1949522323 @default.
• W4226145885 cites W1976731473 @default.
• W4226145885 cites W1982499150 @default.
• W4226145885 cites W1988673699 @default.
• W4226145885 cites W1989607865 @default.
• W4226145885 cites W1998203489 @default.
• W4226145885 cites W1999563094 @default.
• W4226145885 cites W2003426511 @default.
• W4226145885 cites W2006890919 @default.
• W4226145885 cites W2013204606 @default.
• W4226145885 cites W2015391530 @default.
• W4226145885 cites W2025617594 @default.
• W4226145885 cites W2028522806 @default.
• W4226145885 cites W2028818779 @default.
• W4226145885 cites W2030262151 @default.
• W4226145885 cites W2040499359 @default.
• W4226145885 cites W2063437420 @default.
• W4226145885 cites W2071356679 @default.
• W4226145885 cites W2075312652 @default.
• W4226145885 cites W2079701909 @default.
• W4226145885 cites W2082724695 @default.
• W4226145885 cites W2098165352 @default.
• W4226145885 cites W2104135721 @default.
• W4226145885 cites W2109799459 @default.
• W4226145885 cites W2111404870 @default.
• W4226145885 cites W2137256580 @default.
• W4226145885 cites W2144420455 @default.
• W4226145885 cites W2155719750 @default.
• W4226145885 cites W2171193618 @default.
• W4226145885 cites W2184263670 @default.
• W4226145885 cites W2184927026 @default.
• W4226145885 cites W2187552273 @default.
• W4226145885 cites W2304770172 @default.
• W4226145885 cites W2326926590 @default.
• W4226145885 cites W2332154751 @default.
• W4226145885 cites W2416845977 @default.
• W4226145885 cites W2460940568 @default.
• W4226145885 cites W2482194704 @default.
• W4226145885 cites W2557883191 @default.
• W4226145885 cites W2731556531 @default.
• W4226145885 cites W2747950677 @default.
• W4226145885 cites W2750721430 @default.
• W4226145885 cites W2770940524 @default.
• W4226145885 cites W2801530040 @default.
• W4226145885 cites W2805609856 @default.
• W4226145885 cites W2808211602 @default.
• W4226145885 cites W2898789672 @default.
• W4226145885 cites W2915554805 @default.
• W4226145885 cites W2931049698 @default.
• W4226145885 cites W2991352312 @default.
• W4226145885 cites W2999304916 @default.
• W4226145885 cites W3045038985 @default.
• W4226145885 cites W3094034630 @default.
• W4226145885 cites W3111667529 @default.
• W4226145885 cites W3138075043 @default.
• W4226145885 cites W3159826075 @default.
• W4226145885 cites W3182404821 @default.
• W4226145885 cites W3187030826 @default.
• W4226145885 cites W3198897305 @default.
• W4226145885 cites W3207791129 @default.
• W4226145885 cites W4200419030 @default.
• W4226145885 cites W4200602081 @default.
• W4226145885 cites W4221067551 @default.
• W4226145885 cites W4282590808 @default.
• W4226145885 doi "https://doi.org/10.1101/2022.04.05.487130" @default.
• W4226145885 hasPublicationYear "2022" @default.
• W4226145885 type Work @default.
• W4226145885 citedByCount "0" @default.
• W4226145885 crossrefType "posted-content" @default.
• W4226145885 hasAuthorship W4226145885A5019272527 @default.
• W4226145885 hasAuthorship W4226145885A5023205638 @default.
• W4226145885 hasAuthorship W4226145885A5026570144 @default.
• W4226145885 hasAuthorship W4226145885A5033020273 @default.
• W4226145885 hasAuthorship W4226145885A5036634814 @default.
• W4226145885 hasAuthorship W4226145885A5053687021 @default.
• W4226145885 hasAuthorship W4226145885A5061573562 @default.
• W4226145885 hasAuthorship W4226145885A5064412163 @default.
• W4226145885 hasAuthorship W4226145885A5085631360 @default.
• W4226145885 hasBestOaLocation W42261458851 @default.
• W4226145885 hasConcept C104317684 @default.
• W4226145885 hasConcept C126749454 @default.
• W4226145885 hasConcept C145103041 @default.
• W4226145885 hasConcept C196843134 @default.

• next