FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2565463350> ?p ?o ?g. }

• W2565463350 abstract "Insulinomas are well-differentiated pancreatic endocrine tumors that cause abnormal beta cell proliferation and hyperinsulinimic hypoglycemia. With an incidence of 2-4 cases per million per year, insulinomas are rare in adults and even less common in children. Since congenital focal hyperinsulinism, another developmental lesion, is associated with paternal isodisomy for the imprinted 11p15 locus, we sought to characterize the role of this region and of mutations in MEN1 on 11q13 in pediatric insulinoma cases. We identified 13 pediatric insulinoma cases, which is the largest pediatric series reported, and performed immunohistochemical analysis for the maternally expressed tumor suppressor marker p57 located in 11p15. Using blood and tumor DNA, we tested 9 candidate genes associated with congenital hyperinsulinism including ABCC8, KCNJ11 and the MEN1 tumor suppressor. We performed methylation analysis of imprint control regions (ICR) that included the paternally expressed IGF2 (ICR1) and maternally expressed CDKN1C (ICR2) located on 11p15 and genome-wide SNP array analysis with tumor DNA. MEN1 mutations were found in 4 cases and suspected in one (MEN1 group); all 5 tumors stained negative for p57 and were hypermethylated at ICR1 and hypomethylated at ICR2 indicating loss of the maternal allele. SNP arrays confirmed loss of heterozygosity (LOH) of entire chromosome 11 in 4 cases. Four out of the 6 remaining non-MEN1 cases also stained negative for p57; in confirmation, 2 of the 4 cases carried mosaic copy number abnormality of chromosome 11. SNP array data demonstrated extensive genome-wide aneuploidy in MEN1 and non-MEN1 cases; however interstitial changes were not present in any of the cases. Notably, MEN1 cases carried only entire chromosome changes, while non-MEN1 cases carried whole arm changes in addition whole chromosome changes. In conclusion, MEN1 mutations are more common in pediatric insulinomas than in adult insulinoma cases (40% in this study vs. 8% in adults). Compared to adult cases, our pediatric insulinoma cases had smaller sized tumors and a shorter median duration of symptoms, suggesting that these tumors are rapidly growing and that the most common chromosome gains and losses very likely represent early events in insulinoma development. Mechanistically, our data suggest that loss of p57 expression, in conjunction with loss of either MEN1 and/or additional imprinted genes on 11p, play a role in the pathogenesis of most insulinomas. In cases with a germ-line MEN1 mutation, we identified a previously unreported paternal parent-of-origin effect that is unique to pediatric insulinomas but not to other MEN1 endocrine tumors (e.g., prolactinoma, parathyroid adenoma). Since a congenital focal hyperinsulinism has a similar parent of origin effect this suggests a broader role for the imprinted locus, 11p15, in not just the pathogenesis of pediatric insulinomas but also in beta-cell replication. Citation Format: Arupa Ganguly, Tricia Bhatti, Karthik Ganapathy, Laura Conlin, Courtney MacMullen, Susan Becker, Eduardo Ruchelli, Charles Stanley. Molecular evidence for a parent of origin effect in pediatric insulinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3293. doi:10.1158/1538-7445.AM2015-3293" @default.
• W2565463350 created "2017-01-06" @default.
• W2565463350 creator A5012775138 @default.
• W2565463350 creator A5017273578 @default.
• W2565463350 creator A5042649429 @default.
• W2565463350 creator A5049699006 @default.
• W2565463350 creator A5064645355 @default.
• W2565463350 creator A5073631988 @default.
• W2565463350 creator A5082184763 @default.
• W2565463350 creator A5087682597 @default.
• W2565463350 date "2015-08-01" @default.
• W2565463350 modified "2023-09-27" @default.
• W2565463350 title "Abstract 3293: Molecular evidence for a parent of origin effect in pediatric insulinomas" @default.
• W2565463350 doi "https://doi.org/10.1158/1538-7445.am2015-3293" @default.
• W2565463350 hasPublicationYear "2015" @default.
• W2565463350 type Work @default.
• W2565463350 sameAs 2565463350 @default.
• W2565463350 citedByCount "0" @default.
• W2565463350 crossrefType "proceedings-article" @default.
• W2565463350 hasAuthorship W2565463350A5012775138 @default.
• W2565463350 hasAuthorship W2565463350A5017273578 @default.
• W2565463350 hasAuthorship W2565463350A5042649429 @default.
• W2565463350 hasAuthorship W2565463350A5049699006 @default.
• W2565463350 hasAuthorship W2565463350A5064645355 @default.
• W2565463350 hasAuthorship W2565463350A5073631988 @default.
• W2565463350 hasAuthorship W2565463350A5082184763 @default.
• W2565463350 hasAuthorship W2565463350A5087682597 @default.
• W2565463350 hasConcept C104317684 @default.
• W2565463350 hasConcept C122060243 @default.
• W2565463350 hasConcept C134018914 @default.
• W2565463350 hasConcept C13514818 @default.
• W2565463350 hasConcept C135763542 @default.
• W2565463350 hasConcept C142724271 @default.
• W2565463350 hasConcept C143589142 @default.
• W2565463350 hasConcept C153209595 @default.
• W2565463350 hasConcept C180754005 @default.
• W2565463350 hasConcept C2775858560 @default.
• W2565463350 hasConcept C2777368190 @default.
• W2565463350 hasConcept C2777391703 @default.
• W2565463350 hasConcept C2777643638 @default.
• W2565463350 hasConcept C2778764654 @default.
• W2565463350 hasConcept C2779306644 @default.
• W2565463350 hasConcept C2779469564 @default.
• W2565463350 hasConcept C2780053029 @default.
• W2565463350 hasConcept C2780103800 @default.
• W2565463350 hasConcept C2780668416 @default.
• W2565463350 hasConcept C501734568 @default.
• W2565463350 hasConcept C502942594 @default.
• W2565463350 hasConcept C54355233 @default.
• W2565463350 hasConcept C71924100 @default.
• W2565463350 hasConcept C86803240 @default.
• W2565463350 hasConceptScore W2565463350C104317684 @default.
• W2565463350 hasConceptScore W2565463350C122060243 @default.
• W2565463350 hasConceptScore W2565463350C134018914 @default.
• W2565463350 hasConceptScore W2565463350C13514818 @default.
• W2565463350 hasConceptScore W2565463350C135763542 @default.
• W2565463350 hasConceptScore W2565463350C142724271 @default.
• W2565463350 hasConceptScore W2565463350C143589142 @default.
• W2565463350 hasConceptScore W2565463350C153209595 @default.
• W2565463350 hasConceptScore W2565463350C180754005 @default.
• W2565463350 hasConceptScore W2565463350C2775858560 @default.
• W2565463350 hasConceptScore W2565463350C2777368190 @default.
• W2565463350 hasConceptScore W2565463350C2777391703 @default.
• W2565463350 hasConceptScore W2565463350C2777643638 @default.
• W2565463350 hasConceptScore W2565463350C2778764654 @default.
• W2565463350 hasConceptScore W2565463350C2779306644 @default.
• W2565463350 hasConceptScore W2565463350C2779469564 @default.
• W2565463350 hasConceptScore W2565463350C2780053029 @default.
• W2565463350 hasConceptScore W2565463350C2780103800 @default.
• W2565463350 hasConceptScore W2565463350C2780668416 @default.
• W2565463350 hasConceptScore W2565463350C501734568 @default.
• W2565463350 hasConceptScore W2565463350C502942594 @default.
• W2565463350 hasConceptScore W2565463350C54355233 @default.
• W2565463350 hasConceptScore W2565463350C71924100 @default.
• W2565463350 hasConceptScore W2565463350C86803240 @default.
• W2565463350 hasLocation W25654633501 @default.
• W2565463350 hasOpenAccess W2565463350 @default.
• W2565463350 hasPrimaryLocation W25654633501 @default.
• W2565463350 hasRelatedWork W1519708036 @default.
• W2565463350 hasRelatedWork W1974602042 @default.
• W2565463350 hasRelatedWork W1991254948 @default.
• W2565463350 hasRelatedWork W2003546726 @default.
• W2565463350 hasRelatedWork W2006926223 @default.
• W2565463350 hasRelatedWork W2015104323 @default.
• W2565463350 hasRelatedWork W2018197740 @default.
• W2565463350 hasRelatedWork W2038776453 @default.
• W2565463350 hasRelatedWork W2052847071 @default.
• W2565463350 hasRelatedWork W2071271294 @default.
• W2565463350 hasRelatedWork W2092938633 @default.
• W2565463350 hasRelatedWork W2104637577 @default.
• W2565463350 hasRelatedWork W2120960711 @default.
• W2565463350 hasRelatedWork W2138259892 @default.
• W2565463350 hasRelatedWork W2151428293 @default.
• W2565463350 hasRelatedWork W2159891020 @default.
• W2565463350 hasRelatedWork W2160983559 @default.
• W2565463350 hasRelatedWork W2319551347 @default.
• W2565463350 hasRelatedWork W2464182478 @default.
• W2565463350 hasRelatedWork W2921826227 @default.
• W2565463350 isParatext "false" @default.
• W2565463350 isRetracted "false" @default.

• next