ArticleProceedings of the National Academy of Sciences of the United States of America2015
Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 71 citations in OpenAlex.
- Long-term survival and molecular heterogeneity of sporadic multifocal non-functional pancreatic neuroendocrine tumors.iScience · 2026Article
- Molecular Basis of Pancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2024Review
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Implications of noncoding regulatory functions in the development of insulinomas.Cell genomics · 2024Article
- Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?Endocrine pathology · 2024Review
- Causal network perturbation analysis identifies known and novel type-2 diabetes driver genes.bioRxiv : the preprint server for biology · 2024Article
- Role of YY1 in the Regulation of Anti-Apoptotic Gene Products in Drug-Resistant Cancer Cells.Cancers · 2023Review
- An Insight on Functioning Pancreatic Neuroendocrine Neoplasms.Biomedicines · 2023Review
- The Transcription Factor YY1 Is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-Cells.Diabetes · 2022Article
- YY1 Regulates Glucose Homeostasis Through Controlling Insulin Transcription in Pancreatic β-Cells.Diabetes · 2022Article
- Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy.Frontiers in oncology · 2022Review
- Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review.Cell & bioscience · 2021Review
- New Regions With Molecular Alterations in a Rare Case of Insulinomatosis: Case Report With Literature Review.Frontiers in endocrinology · 2021Review
- Article
- Molecular Signatures and Their Clinical Utility in Pancreatic Neuroendocrine Tumors.Frontiers in endocrinology · 2020Review
- Calcium Permeable Channels in Cancer Hallmarks.Frontiers in pharmacology · 2020Review
- Article
- Clinical applications of (epi)genetics in gastroenteropancreatic neuroendocrine neoplasms: Moving towards liquid biopsies.Reviews in endocrine & metabolic disorders · 2019Review
- Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging.Journal of cellular physiology · 2019Article
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
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 Ca(2+) channel); both are expressed at very low levels in normal β-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 Ca(2+) signaling pathways involved in insulin secretion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.