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Neomorphic effects ...
Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas
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Cromer, M. Kyle (author)
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Choi, Murim (author)
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Nelson-Williams, Carol (author)
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Fonseca, Annabelle L. (author)
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Kunstman, John W. (author)
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Korah, Reju M. (author)
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Overton, John D. (author)
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Mane, Shrikant (author)
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Kenney, Barton (author)
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Malchoff, Carl D. (author)
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- Stålberg, Peter (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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- Åkerström, Göran (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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- Westin, Gunnar (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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- Hellman, Per (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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Carling, Tobias (author)
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- Björklund, Peyman (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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Lifton, Richard P. (author)
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(creator_code:org_t)
- 2015-03-18
- 2015
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:13, s. 4062-4067
- Related links:
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https://doi.org/10.1...
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca2+ channel); both are expressed at very low levels in normal beta-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca2+ signaling pathways involved in insulin secretion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- exome sequencing
- insulinoma
- YY1
- cAMP
- adenylyl cyclase
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Cromer, M. Kyle
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Choi, Murim
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Nelson-Williams, ...
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Fonseca, Annabel ...
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Kunstman, John W ...
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Korah, Reju M.
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show more...
-
Overton, John D.
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Mane, Shrikant
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Kenney, Barton
-
Malchoff, Carl D ...
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Stålberg, Peter
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Åkerström, Göran
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Westin, Gunnar
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Hellman, Per
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Carling, Tobias
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Björklund, Peyma ...
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Lifton, Richard ...
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Uppsala University