SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:uu-223640"
 

Search: onr:"swepub:oai:DiVA.org:uu-223640" > Recurrent activatin...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Goh, Gerald (author)

Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-04-20
  • Springer Science and Business Media LLC,2014
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-223640
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-223640URI
  • https://doi.org/10.1038/ng.2956DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Correction in: Nature Genetics, vol. 46, article nr. 759 (2014), doi: 10.1038/ng0714-759b
  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Scholl, Ute (author)
  • Healy, James (author)
  • Choi, Murim (author)
  • Prasad, Manju L (author)
  • Nelson-Williams, Carol (author)
  • Kuntsman, John W (author)
  • Korah, Reju (author)
  • Suttorp, Anna-Carinna (author)
  • Dietrich, Dimo (author)
  • Haase, Mathias (author)
  • Willenberg, Holger S (author)
  • Stålberg, PeterUppsala universitet,Endokrinkirurgi(Swepub:uu)petestah (author)
  • Hellman, PerUppsala universitet,Endokrinkirurgi(Swepub:uu)perhellm (author)
  • Åkerström, GöranUppsala universitet,Endokrinkirurgi(Swepub:uu)goranas (author)
  • Björklund, PeymanUppsala universitet,Experimentell kirurgi(Swepub:uu)pebjo957 (author)
  • Carling, Tobias (author)
  • Lifton, Richard P (author)
  • Uppsala universitetEndokrinkirurgi (creator_code:org_t)

Related titles

  • In:Nature Genetics: Springer Science and Business Media LLC46:6, s. 613-6171061-40361546-1718

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view