{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:05Z","timestamp":1784557205634,"version":"3.55.0"},"reference-count":65,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T00:00:00Z","timestamp":1442966400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/deed.en_GB"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>\n                    Overexpression of\n                    <jats:italic>insulin growth factor 2<\/jats:italic>\n                    (\n                    <jats:italic>IGF2<\/jats:italic>\n                    ) is a hallmark of adrenocortical carcinomas and pheochromocytomas. Previous studies investigating the\n                    <jats:italic>IGF2\/H19<\/jats:italic>\n                    locus have mainly focused on a single molecular level such as genomic alterations or altered DNA methylation levels and the causal changes underlying\n                    <jats:italic>IGF2<\/jats:italic>\n                    overexpression are still not fully established. In the current study, we analyzed 62 tumors of the adrenal gland from patients with Conn's adenoma (CA,\n                    <jats:italic>n<\/jats:italic>\n                    =12), pheochromocytomas (PCC,\n                    <jats:italic>n<\/jats:italic>\n                    =10), adrenocortical benign tumors (ACBT,\n                    <jats:italic>n<\/jats:italic>\n                    =20), and adrenocortical carcinomas (ACC,\n                    <jats:italic>n<\/jats:italic>\n                    =20). Gene expression, somatic copy number variation of chr11p15.5, and DNA methylation status of three differential methylated regions of the\n                    <jats:italic>IGF2\/H19<\/jats:italic>\n                    locus including the\n                    <jats:italic>H19<\/jats:italic>\n                    imprinting control region were integratively analyzed.\n                    <jats:italic>IGF2<\/jats:italic>\n                    overexpression was found in 85% of the ACCs and 100% of the PCCs compared to 23% observed in CAs and ACBTs. Copy number aberrations of chr11p15.5 were abundant in both PCCs and ACCs but while PCCs retained a diploid state, ACCs were frequently tetraploid (7\/19). Loss of either a single allele or loss of two alleles of the same parental origin in tetraploid samples resulted in a uniparental disomy-like genotype. These copy number changes correlated with hypermethylation of the\n                    <jats:italic>H19<\/jats:italic>\n                    ICR suggesting that the lost alleles were the unmethylated maternal alleles. Our data provide conclusive evidence that loss of the maternal allele correlates with\n                    <jats:italic>IGF2<\/jats:italic>\n                    overexpression in adrenal tumors and that hypermethylation of the\n                    <jats:italic>H19<\/jats:italic>\n                    ICR is a consequence thereof.\n                  <\/jats:p>","DOI":"10.1530\/erc-15-0086","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T22:09:04Z","timestamp":1443046144000},"page":"953-967","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":26,"title":["Copy number variations alter methylation and parallel IGF2 overexpression in adrenal tumors"],"prefix":"10.1530","volume":"22","author":[{"given":"Helene Myrtue","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"How-Kit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Guerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Castinetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Kristian Moen","family":"Vollan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"De Micco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Daunay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Taieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Van Loo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Besse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vessela N","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise Lotte","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Barlier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Sebag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Tost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2015110216263299000_22.6.953.1","doi-asserted-by":"crossref","unstructured":"Akhtar M Holmgren C Gondor A Vesterlund M Kanduri C Larsson C Ekstrom TJ 2012 Cell type and context-specific function of PLAG1 for IGF2 P3 promoter activity. 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