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Somatic mutation of CDKN1B in small intestine neuroendocrine tumors

by Kanwar, Rahul , Sougnez, Carrie , Pho, Nam , Thirlwell, Christina , Caplin, Martyn , Pugh, Trevor , Meyer, Tim , Shefler, Erica , Harris, Chris R , Beutler, Andreas S , Shivdasani, Ramesh , Hooshmand, Susanne M , Kiezun, Adam , McKenna, Aaron , Kulke, Matthew , Ogino, Shuji , Contractor, Tanupriya , Francis, Joshua M , Ojesina, Akinyemi I , Lennon, Niall , Serra, Stefano , Qian, Zhi Rong , Auclair, Daniel , Green, Lisa , Pedamallu, Chandra Sekhar , Sivachenko, Andrey , Asa, Sylvia L , Brais, Lauren K , Saksena, Gordon , Grimsby, Jonna , Carter, Scott L , Karpathakis, Anna , Onofrio, Robert , Cibulskis, Kristian , Voet, Douglas , Manzo, Veronica , Philips, Juliet , Lawrence, Michael S , Meyerson, Matthew , Freeman, Samuel , Banck, Michaela S , Kulkarni, Amit A , Jones, Robert T , Chung, Daniel C , Ramos, Alex H , Getz, Gad , Nickerson, Elizabeth

in 45 / 45/23 / 631/208 / 631/208/212 / 692/308/2056 / 692/699/1503/1504 / Agriculture / Animal Genetics and Genomics / Biomedicine / Cancer Research / Cell cycle / Cell Cycle - genetics / Cellular control mechanisms / Chromosomes / Cohort Studies / Cyclin-Dependent Kinase Inhibitor p27 - genetics / Gastrointestinal tumors / Gene Function / Gene mutations / Genes / Genes, Tumor Suppressor / Genetic aspects / Genetic Predisposition to Disease / Human Genetics / Humans / Identification and classification / Intestinal Neoplasms - epidemiology / Intestinal Neoplasms - genetics / Intestinal Neoplasms - pathology / Intestine, Small - pathology / Kinases / letter / Mutation / Neuroendocrine Tumors - epidemiology / Neuroendocrine Tumors - genetics / Neuroendocrine Tumors - pathology / Rodents / Sequence Analysis, DNA / Tumor suppressor genes

2013

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2013

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2013

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Journal Article

Somatic mutation of CDKN1B in small intestine neuroendocrine tumors

Kanwar, Rahul,

Sougnez, Carrie,

Pho, Nam,

Thirlwell, Christina,

Caplin, Martyn,

Pugh, Trevor,

Meyer, Tim,

Shefler, Erica,

Harris, Chris R,

Beutler, Andreas S,

Shivdasani, Ramesh,

Hooshmand, Susanne M,

Kiezun, Adam,

McKenna, Aaron,

Kulke, Matthew,

Ogino, Shuji,

Contractor, Tanupriya,

Francis, Joshua M,

Ojesina, Akinyemi I,

Lennon, Niall,

Serra, Stefano,

Qian, Zhi Rong,

Auclair, Daniel,

Green, Lisa,

Pedamallu, Chandra Sekhar,

Sivachenko, Andrey,

Asa, Sylvia L,

Brais, Lauren K,

Saksena, Gordon,

Grimsby, Jonna,

Carter, Scott L,

Karpathakis, Anna,

Onofrio, Robert,

Cibulskis, Kristian,

Voet, Douglas,

Manzo, Veronica,

Philips, Juliet,

Lawrence, Michael S,

Meyerson, Matthew,

Freeman, Samuel,

Banck, Michaela S,

Kulkarni, Amit A,

Jones, Robert T,

Chung, Daniel C,

Ramos, Alex H,

Getz, Gad,

Nickerson, Elizabeth

2013

Overview

Matthew Meyerson and colleagues report whole-exome and whole-genome sequencing of 55 small intestine neuroendocrine tumors. They identify recurrent somatic mutations in CDKN1B , implicating cell cycle dysregulation in the pathogenesis of these tumors. 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.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

/ 45/23

/ 631/208

/ Animal Genetics and Genomics