{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:23:03Z","timestamp":1783606983016,"version":"3.55.0"},"reference-count":47,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":45,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Beckwith\u2013Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth and tumor predisposition, caused by dysregulated expression of genes on chromosome 11p15.5. An association between BWS and pheochromocytoma\/paraganglioma (PPGL) has been suggested in isolated case reports over the past fifty years, but the molecular basis for this link remains unclear. We identified four patients with BWS who developed metastatic PPGL and investigated IGF2 pathway activation in these tumors and in PPGL across various genotypes. Pan-cancer transcriptomic analysis of The Cancer Genome Atlas (TCGA) demonstrated that PPGL overexpresses IGF2, with pseudohypoxic tumors exhibiting higher expression compared to other molecular clusters. Loss of heterozygosity and loss of imprinting at 11p15.5 partially explain this overexpression, with PPGL additionally demonstrating globally elevated expression of imprinted genes compared to most other tumor types, suggesting a broader relaxation of genomic imprinting. Cognate receptor profiling revealed that PPGLs are equipped to respond to IGF2 signaling, with high expression of IGF1R and insulin receptor isoform A (IR-A). Immunohistochemistry confirmed IGF2 protein overexpression in both BWS-associated and genotypically diverse sporadic PPGLs. Our results indicate that IGF2 overexpression is a convergent molecular feature of PPGL across genotypes and suggest the IGF2 pathway as a potential diagnostic and therapeutic target.<\/jats:p>","DOI":"10.1530\/erc-26-0061","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:43:57Z","timestamp":1778521437000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Convergent IGF2 overexpression in pheochromocytoma\/paraganglioma: insights from Beckwith\u2013Wiedemann syndrome"],"prefix":"10.1530","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-9348","authenticated-orcid":true,"given":"Hussam","family":"Alkaissi","sequence":"first","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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