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Nat Genet DOI:10.1038/ng.2821

Somatic mutation of CDKN1B in small intestine neuroendocrine tumors.

Publication TypeJournal Article
Year of Publication2013
AuthorsFrancis, JM, Kiezun, A, Ramos, AH, Serra, S, Pedamallu, CSekhar, Qian, ZRong, Banck, MS, Kanwar, R, Kulkarni, AA, Karpathakis, A, Manzo, V, Contractor, T, Philips, J, Nickerson, E, Pho, N, Hooshmand, SM, Brais, LK, Lawrence, MS, Pugh, T, McKenna, A, Sivachenko, A, Cibulskis, K, Carter, SL, Ojesina, AI, Freeman, S, Jones, RT, Voet, D, Saksena, G, Auclair, D, Onofrio, R, Shefler, E, Sougnez, C, Grimsby, J, Green, L, Lennon, N, Meyer, T, Caplin, M, Chung, DC, Beutler, AS, Ogino, S, Thirlwell, C, Shivdasani, R, Asa, SL, Harris, CR, Getz, G, Kulke, M, Meyerson, M
JournalNat Genet
Date Published2013 Dec
KeywordsCell Cycle, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p27, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Intestinal Neoplasms, Intestine, Small, Mutation, Neuroendocrine Tumors, Sequence Analysis, DNA

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.


Alternate JournalNat. Genet.
PubMed ID24185511
PubMed Central IDPMC4239432
Grant List12183 / / Cancer Research UK / United Kingdom
P30 CA015083 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
/ / Cancer Research UK / United Kingdom