Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent hypoglycemia: a diagnostic dilemma

Ramkumar, S; Dhingra, Atul; Jyotsna, Viveka P; Ganie, Mohd Ashraf; Das, Chandan Jyoti; Seth, Amlesh; Sharma, Mehar Chand; Bal, Chandra Sekhar

doi:10.1186/1472-6823-14-36

Cited by 22 publications

(20 citation statements)

References 16 publications

(11 reference statements)

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“…For this reason TC-YIK is sufficiently interesting for the purposes of an investigative study integrating CAGE and ChIP-seq data. Lastly, although there are rare reports of non-islet-cell insulinomas that ectopically express insulin [e.g., kidney (Ramkumar et al, 2014 ), liver (Furrer et al, 2001 ), brain (Nakamura et al, 2001 )] and additional cases of argyrophilic small cell carcinoma (ASCC) of cervix (Kiang et al, 1973 ; Seckl et al, 1999 ), ours is the first report to our knowledge that identifies a non-islet-cell line (TC-YIK) where the majority of the beta cell program is active.…”

Section: Resultsmentioning

confidence: 99%

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

Lizio¹,

Ishizu²,

Itoh

et al. 2015

Front. Genet.

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Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting ChIP-seq datasets. (1) A large fraction of binding sites are at distal enhancer sites and cannot be directly associated to their targets, without chromatin conformation data. (2) Many peaks may be non-functional: even when there is a peak at a promoter, the expression of the gene may not be affected in the matching perturbation experiment.

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Section: Resultsmentioning

confidence: 99%

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

Lizio¹,

Ishizu²,

Itoh

et al. 2015

Front. Genet.

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“…However, the case report caused controversy. Third, other extrapancreatic tumors have been reported to secrete insulin and cause hyperinsulinemic hypoglycemia, including ovarian tumors, cervical carcinoids, kidney carcinoids, paragangliomas and liver neuroendocrine tumors [14, 15]. In this study, these tumors were not classified as an ectopic insulinoma.…”

Section: Resultsmentioning

confidence: 83%

Ectopic insulinoma: case report

et al. 2019

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BackgroundEctopic insulinoma is a rare entity that is difficult to diagnose before surgery. This article reports two cases of ectopic insulinoma.Case presentationTwo patients manifested recurrent hypoglycemia with a typical Whipple triad. In terms of the qualitative diagnosis, the oral glucose tolerance test (OGTT) suggested a diagnosis of hyperinsulinemic hypoglycemia. However, preoperative imaging did not show a significant mass in the pancreas. In one patient, preoperative abdominal enhanced volume perfusion computed tomography (CT), somatostatin receptor imaging and 99mTc-HYNIC-TOC SPECT/CT revealed a mass with a rich blood supply anterior to the duodenum. In the other patient, preoperative enhanced CT, magnetic resonance imaging (MRI) and 68Ga-Exendin-4 PET/CT showed a mass above the spleen. After surgical removal of the tumor, both patients received a confirmed diagnosis of neuroendocrine tumors by postoperative pathology. The symptoms of hypoglycemia were relieved after surgery, and the blood glucose level was significantly increased.ConclusionEctopic insulinoma is difficult to locate before surgery. 68Ga-Exendin-4 PET/CT has a high diagnostic value. Surgical removal of the lesion is main treatment.

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“…Nonislet cell tumors secreting insulin are infrequently reported, and comprise 1%‐2% of insulinomas, 7 most commonly arising in peripancreatic or periduodenal regions. Ectopic insulin secretion has been reported in pheochromocytomas, and NENs of the kidney, liver, ovary, lung, and cervix 7 .…”

Section: Discussionmentioning

confidence: 99%

Ectopic insulin secretion by a large‐cell neuroendocrine carcinoma of the cervix

Wang

Vasey

Varikatt

et al. 2020

Clinical Case Reports

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Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent hypoglycemia: a diagnostic dilemma

Cited by 22 publications

References 16 publications

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

Ectopic insulinoma: case report

Ectopic insulin secretion by a large‐cell neuroendocrine carcinoma of the cervix

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