Sökning: onr:"swepub:oai:DiVA.org:uu-223640" > Recurrent activatin...
Fältnamn | Indikatorer | Metadata |
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000 | 03706naa a2200541 4500 | |
001 | oai:DiVA.org:uu-223640 | |
003 | SwePub | |
008 | 140423s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2236402 URI |
024 | 7 | a https://doi.org/10.1038/ng.29562 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Goh, Gerald4 aut |
245 | 1 0 | a Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors |
264 | c 2014-04-20 | |
264 | 1 | b Springer Science and Business Media LLC,c 2014 |
338 | a print2 rdacarrier | |
500 | a Correction in: Nature Genetics, vol. 46, article nr. 759 (2014), doi: 10.1038/ng0714-759b | |
520 | a Adrenal tumors autonomously producing cortisol cause Cushing's syndrome1, 2, 3, 4. We performed exome sequencing of 25 tumor-normal pairs and identified 2 subgroups. Eight tumors (including three carcinomas) had many somatic copy number variants (CNVs) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2 and protein-altering mutations in TP53 and RB1. Seventeen tumors (all adenomas) had no somatic CNVs or TP53 or RB1 mutations. Six of these had known gain-of-function mutations in CTNNB1 (β-catenin)5, 6 or GNAS (Gαs)7, 8. Six others had somatic mutations in PRKACA (protein kinase A (PKA) catalytic subunit) resulting in a p.Leu206Arg substitution. Further sequencing identified this mutation in 13 of 63 tumors (35% of adenomas with overt Cushing's syndrome). PRKACA, GNAS and CTNNB1 mutations were mutually exclusive. Leu206 directly interacts with the regulatory subunit of PKA, PRKAR1A9, 10. Leu206Arg PRKACA loses PRKAR1A binding, increasing the phosphorylation of downstream targets. PKA activity induces cortisol production and cell proliferation11, 12, 13, 14, 15, providing a mechanism for tumor development. These findings define distinct mechanisms underlying adrenal cortisol-producing tumors. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kirurgi0 (SwePub)302122 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Surgery0 (SwePub)302122 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
700 | 1 | a Scholl, Ute4 aut |
700 | 1 | a Healy, James4 aut |
700 | 1 | a Choi, Murim4 aut |
700 | 1 | a Prasad, Manju L4 aut |
700 | 1 | a Nelson-Williams, Carol4 aut |
700 | 1 | a Kuntsman, John W4 aut |
700 | 1 | a Korah, Reju4 aut |
700 | 1 | a Suttorp, Anna-Carinna4 aut |
700 | 1 | a Dietrich, Dimo4 aut |
700 | 1 | a Haase, Mathias4 aut |
700 | 1 | a Willenberg, Holger S4 aut |
700 | 1 | a Stålberg, Peteru Uppsala universitet,Endokrinkirurgi4 aut0 (Swepub:uu)petestah |
700 | 1 | a Hellman, Peru Uppsala universitet,Endokrinkirurgi4 aut0 (Swepub:uu)perhellm |
700 | 1 | a Åkerström, Göranu Uppsala universitet,Endokrinkirurgi4 aut0 (Swepub:uu)goranas |
700 | 1 | a Björklund, Peymanu Uppsala universitet,Experimentell kirurgi4 aut0 (Swepub:uu)pebjo957 |
700 | 1 | a Carling, Tobias4 aut |
700 | 1 | a Lifton, Richard P4 aut |
710 | 2 | a Uppsala universitetb Endokrinkirurgi4 org |
773 | 0 | t Nature Geneticsd : Springer Science and Business Media LLCg 46:6, s. 613-617q 46:6<613-617x 1061-4036x 1546-1718 |
856 | 4 | u https://europepmc.org/articles/pmc4074779?pdf=render |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-223640 |
856 | 4 8 | u https://doi.org/10.1038/ng.2956 |
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