title: Somatic mutation of CDKN1B in small intestine neuroendocrine tumors.
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.
authors.affiliation: 1] Broad Institute, Cambridge, Massachusetts, USA. [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3].
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Francis
authors.forename: Adam
authors.initials: A
authors.lastname: Kiezun
authors.forename: Alex H
authors.initials: AH
authors.lastname: Ramos
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
authors.forename: Chandra Sekhar
authors.initials: CS
authors.lastname: Pedamallu
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.forename: Michaela S
authors.initials: MS
authors.lastname: Banck
authors.forename: Rahul
authors.initials: R
authors.lastname: Kanwar
authors.forename: Amit A
authors.initials: AA
authors.lastname: Kulkarni
authors.forename: Anna
authors.initials: A
authors.lastname: Karpathakis
authors.forename: Veronica
authors.initials: V
authors.lastname: Manzo
authors.forename: Tanupriya
authors.initials: T
authors.lastname: Contractor
authors.forename: Juliet
authors.initials: J
authors.lastname: Philips
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nickerson
authors.forename: Nam
authors.initials: N
authors.lastname: Pho
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Hooshmand
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Brais
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.forename: Trevor
authors.initials: T
authors.lastname: Pugh
authors.forename: Aaron
authors.initials: A
authors.lastname: McKenna
authors.forename: Andrey
authors.initials: A
authors.lastname: Sivachenko
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.forename: Akinyemi I
authors.initials: AI
authors.lastname: Ojesina
authors.forename: Samuel
authors.initials: S
authors.lastname: Freeman
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jones
authors.forename: Douglas
authors.initials: D
authors.lastname: Voet
authors.forename: Gordon
authors.initials: G
authors.lastname: Saksena
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.forename: Robert
authors.initials: R
authors.lastname: Onofrio
authors.forename: Erica
authors.initials: E
authors.lastname: Shefler
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.forename: Jonna
authors.initials: J
authors.lastname: Grimsby
authors.forename: Lisa
authors.initials: L
authors.lastname: Green
authors.forename: Niall
authors.initials: N
authors.lastname: Lennon
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
authors.forename: Martyn
authors.initials: M
authors.lastname: Caplin
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chung
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Beutler
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.forename: Christina
authors.initials: C
authors.lastname: Thirlwell
authors.forename: Ramesh
authors.initials: R
authors.lastname: Shivdasani
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.forename: Chris R
authors.initials: CR
authors.lastname: Harris
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Matthew
authors.initials: M
authors.lastname: Kulke
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D015331:Cohort Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D007414:Intestinal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27