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Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 2013 Dec;45(12):1483-6

Date

11/05/2013

Pubmed ID

24185511

Pubmed Central ID

PMC4239432

DOI

10.1038/ng.2821

Scopus ID

2-s2.0-84888369188 (requires institutional sign-in at Scopus site)   298 Citations

Abstract

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.

Author List

Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, 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

Author

Akinyemi Ojesina PhD, MBBS Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell 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