The diagnosed incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, and the underlying genomic mechanisms have not yet been defined. Using exome-and genome-sequence analysis of SI-NETs, we identified recurrent somatic mutations and deletions in CDKN1B, the cyclin-dependent kinase inhibitor gene, which encodes p27. We observed frameshift mutations of CDKN1B in 14 of 180 SI-NETs, and we detected hemizygous deletions encompassing CDKN1B in 7 out of 50 SI-NETs, nominating p27 as a tumor suppressor and implicating cell cycle dysregulation in the etiology of SI-NETs.
Bibliographical noteFunding Information:
This work was supported by grants from the Caring for Carcinoid Foundation (S.L.A. and M.M.), the Raymond and Beverly Sackler Foundation for the Arts and Sciences (C.T., A. Karpathakis, S.L.A. and M.M.) and Cancer Research UK (C.T. and A. Karpathakis).
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