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Delemer, B.* ; Florea, S.M.* ; Decoudier, B.* ; Boulagnon-Rombi, C.* ; Karna, B. ; Pellegata, N.S. ; Buffet, A.* ; Beckers, A.* ; Petrossians, P.* ; Daly, A.F.*

Loss of heterozygosity and absence of MAX immunostaining in a prolactinoma associated with multiple endocrine neoplasia type 5 (MEN5).

Pituitary 28:127 (2025)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
BACKGROUND: Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome caused by germline pathogenic variants involving the MYC Associated Factor X (MAX) gene. Affected individuals typically have pheochromocytomas, often bilateral, at a relatively early age. In MAX pheochromocytoma cohorts, pituitary adenomas are rarely reported. The role of MAX as a tumor suppressor gene in the pituitary gland has not been directly proven to date. METHODS: The propositus came from a pheochromocytoma kindred with a germline pathogenic MAX variant c.97 C>T (p.R33*). In his late thirties he developed asynchronous bilateral pheochromocytomas and underwent bilateral adrenalectomy. At age 46, he developed hyperprolactinemia (45.1 μg/L; 3x ULN) and increased IGF-1 (460 ng/mL; 1.9x ULN). Total testosterone was low (1.5 ng/mL) as was LH (1.2 IU/L). Pituitary MRI showed a microadenoma (6 mm), which was resected and his prolactin, IGF-1, and testosterone levels normalized. A Pituitary adenoma was confirmed on pathology, which showed positivity for prolactin only and a Ki67 of 2%. RESULTS: MAX immunohistochemical staining was lost in the pituitary adenoma cells. Tumoral DNA analysis (120X read depth) showed that at the MAX locus the pathogenic variant c.97 C>T constituted > 90% of the sequencing reads supporting tumoral loss of heterozygosity (LOH). CONCLUSIONS: Loss of MAX staining and the identification of tumor LOH at the MAX locus confirms pituitary adenomas as a component tumor in the emerging MEN5 syndrome due to germline pathogenic MAX variants.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetics ; Max ; Men5 ; Pheochromocytoma ; Pituitary Adenoma; Mutations; Pheochromocytoma; Hereditary; Protein; Network; Complex
ISSN (print) / ISBN 1386-341X
e-ISSN 1573-7403
Zeitschrift Pituitary
Quellenangaben Band: 28, Heft: 6, Seiten: , Artikelnummer: 127 Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)