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Overexpression of Cyclin D1 Occurs Frequently in Human Pancreatic Endocrine Tumors¹

Gastrointestinal Unit and Department of Medicine (D.C.C.), Department of Pathology (F.G.-C.), Department of Surgery (A.L.W.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Center for Molecular Medicine (S.B.B., A.A.), University of Connecticut Health Center, Farmington, Connecticut 06030; Laboratory of Chemotherapy (M.S.), Aichi Cancer Center, Nagoya, Japan; and Digestive Diseases Branch (R.T.J.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Daniel C. Chung, Gastrointestinal Unit, GRJ 825, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: d_chung{at}helix.mgh.harvard.edu

The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G₁/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional.

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