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Lichtenauer, U.D.* ; di Dalmazi, G.* ; Slater, E.P.* ; Wieland, T. ; Kuebart, A.* ; Schmittfull, A. ; Schwarzmayr, T. ; Diener, S. ; Wiese, D.* ; Thasler, W.E.* ; Reincke, M.* ; Meitinger, T. ; Schott, M.* ; Fassnacht, M.* ; Bartsch, D.K.* ; Strom, T.M. ; Beuschlein, F.*

Frequency and clinical correlates of somatic Ying Yang 1 mutations in sporadic insulinomas.

J. Clin. Endocrinol. Metab. 100, E776-E782 (2015)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
CONTEXT: Insulinomas represent pancreatic neuroendocrine neoplasms (pNEN) that cause severe morbidity attributed to their often pronounced endocrine activity. Apart from hereditary forms such as MEN-1, genetic causes for sporadic insulinoma development had remained obscure until recently. Applying next generation sequencing methods, disease causing genetic alterations have been identified in various endocrine tumors. OBJECTIVE: and Design: Tumor- and matched blood DNA from 8 patients with sporadic insulinomas (5 females and 2 malignant) were analyzed by whole exome sequencing. Following this initial analysis, Ying Yang 1 (YY1) mutation status was assessed in a larger cohort of 39 additional insulinomas (including 8 malignant and 1 liver metastasis) from 3 German hospitals by targeted sequencing. The mutation status was correlated with various clinical parameters. RESULTS: A range of 1 - 12 somatic genetic variants were identified by exome sequencing. A recurrent somatic Thr372Arg YY1 point mutation was detected in 2 patients of the initial and in 4 patients of the second cohort (total 6/47; 13 %). Presence of the mutation was associated with a trend towards higher age (62±13 vs. 48±17; p=0.06) and all affected patients were females (6/6, p=0.04). All other clinical parameters, including presence of malignancy and metastatic spread, tumor localization, and hypoglycemic episodes were not different between YY1 mutated and non-mutated tumor carriers. CONCLUSIONS: The somatic Thr372Arg YY1 mutation is a relevant finding in female patients with sporadic insulinomas. The prevalence of this mutation in this Caucasian population is considerably lower compared to that of a recently described Asian cohort.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pancreatic Endocrine Tumors; Adrenal Cushings-syndrome; Differentiated-neuroendocrine-tumors; Nucleotide Polymorphism Analysis; Aldosterone-producing Adenomas; Enets Consensus Guidelines; Transcription Factor Yy1; Allelic Alterations; Catalytic Subunit; Hypertension
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Quellenangaben Band: 100, Heft: 5, Seiten: E776-E782 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Begutachtungsstatus Peer reviewed