Somatic mutation of CDKN1B in small intestine neuroendocrine tumors

Joshua M. Francis, Adam Kiezun, Alex H. Ramos, Stefano Serra, Chandra Sekhar Pedamallu, Zhi Rong Qian, Michaela S. Banck, Rahul Kanwar, Amit A. Kulkarni, Anna Karpathakis, Veronica Manzo, Tanupriya Contractor, Juliet Philips, Elizabeth Nickerson, Nam Pho, Susanne M. Hooshmand, Lauren K. Brais, Michael S. Lawrence, Trevor Pugh, Aaron McKenna & 27 others Andrey Sivachenko, Kristian Cibulskis, Scott L. Carter, Akinyemi I. Ojesina, Samuel Freeman, Robert T. Jones, Douglas Voet, Gordon Saksena, Daniel Auclair, Robert Onofrio, Erica Shefler, Carrie Sougnez, Jonna Grimsby, Lisa Green, Niall Lennon, Tim Meyer, Martyn Caplin, Daniel C. Chung, Andreas S Beutler, Shuji Ogino, Christina Thirlwell, Ramesh Shivdasani, Sylvia L. Asa, Chris R. Harris, Gad Getz, Matthew Kulke, Matthew Meyerson

Research output: Contribution to journalArticle

132 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1483-1486
Number of pages4
JournalNature Genetics
Volume45
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Neuroendocrine Tumors
Small Intestine
Mutation
Exome
Frameshift Mutation
Cyclin-Dependent Kinases
Sequence Deletion
Sequence Analysis
Cell Cycle
Genome
Incidence
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Francis, J. M., Kiezun, A., Ramos, A. H., Serra, S., Pedamallu, C. S., Qian, Z. R., ... Meyerson, M. (2013). Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nature Genetics, 45(12), 1483-1486. https://doi.org/10.1038/ng.2821

Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. / Francis, Joshua M.; Kiezun, Adam; Ramos, Alex H.; Serra, Stefano; Pedamallu, Chandra Sekhar; Qian, Zhi Rong; Banck, Michaela S.; Kanwar, Rahul; Kulkarni, Amit A.; Karpathakis, Anna; Manzo, Veronica; Contractor, Tanupriya; Philips, Juliet; Nickerson, Elizabeth; Pho, Nam; Hooshmand, Susanne M.; Brais, Lauren K.; Lawrence, Michael S.; Pugh, Trevor; McKenna, Aaron; Sivachenko, Andrey; Cibulskis, Kristian; Carter, Scott L.; Ojesina, Akinyemi I.; Freeman, Samuel; Jones, Robert T.; Voet, Douglas; Saksena, Gordon; Auclair, Daniel; Onofrio, Robert; Shefler, Erica; Sougnez, Carrie; Grimsby, Jonna; Green, Lisa; Lennon, Niall; Meyer, Tim; Caplin, Martyn; Chung, Daniel C.; Beutler, Andreas S; Ogino, Shuji; Thirlwell, Christina; Shivdasani, Ramesh; Asa, Sylvia L.; Harris, Chris R.; Getz, Gad; Kulke, Matthew; Meyerson, Matthew.

In: Nature Genetics, Vol. 45, No. 12, 12.2013, p. 1483-1486.

Research output: Contribution to journalArticle

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 2013, 'Somatic mutation of CDKN1B in small intestine neuroendocrine tumors', Nature Genetics, vol. 45, no. 12, pp. 1483-1486. https://doi.org/10.1038/ng.2821
Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR et al. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nature Genetics. 2013 Dec;45(12):1483-1486. https://doi.org/10.1038/ng.2821
Francis, Joshua M. ; Kiezun, Adam ; Ramos, Alex H. ; Serra, Stefano ; Pedamallu, Chandra Sekhar ; Qian, Zhi Rong ; Banck, Michaela S. ; Kanwar, Rahul ; Kulkarni, Amit A. ; Karpathakis, Anna ; Manzo, Veronica ; Contractor, Tanupriya ; Philips, Juliet ; Nickerson, Elizabeth ; Pho, Nam ; Hooshmand, Susanne M. ; Brais, Lauren K. ; Lawrence, Michael S. ; Pugh, Trevor ; McKenna, Aaron ; Sivachenko, Andrey ; Cibulskis, Kristian ; Carter, Scott L. ; Ojesina, Akinyemi I. ; Freeman, Samuel ; Jones, Robert T. ; Voet, Douglas ; Saksena, Gordon ; Auclair, Daniel ; Onofrio, Robert ; Shefler, Erica ; Sougnez, Carrie ; Grimsby, Jonna ; Green, Lisa ; Lennon, Niall ; Meyer, Tim ; Caplin, Martyn ; Chung, Daniel C. ; Beutler, Andreas S ; Ogino, Shuji ; Thirlwell, Christina ; Shivdasani, Ramesh ; Asa, Sylvia L. ; Harris, Chris R. ; Getz, Gad ; Kulke, Matthew ; Meyerson, Matthew. / Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. In: Nature Genetics. 2013 ; Vol. 45, No. 12. pp. 1483-1486.
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