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; 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

doi:10.1038/ng.2821

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 McKennaAndrey 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

Medical Oncology

Research output: Contribution to journal › Article › peer-review

183 Scopus 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.

Original language	English (US)
Pages (from-to)	1483-1486
Number of pages	4
Journal	Nature Genetics
Volume	45
Issue number	12
DOIs	https://doi.org/10.1038/ng.2821
State	Published - Dec 2013

ASJC Scopus subject areas

Genetics

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Francis, J. M., Kiezun, A., Ramos, A. H., Serra, S., Pedamallu, C. S., Qian, Z. R., Banck, M. S., Kanwar, R., Kulkarni, A. A., Karpathakis, A., Manzo, V., Contractor, T., Philips, J., Nickerson, E., Pho, N., Hooshmand, S. M., Brais, L. K., Lawrence, M. S., Pugh, T., ... 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

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

@article{876299cf524d43d0bfeee4636b273e09,

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.",

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

note = "Funding Information: This work was supported by grants from the Caring for Carcinoid Foundation (S.L.A. and M.M.), the Raymond and Beverly Sackler Foundation for the Arts and Sciences (C.T., A. Karpathakis, S.L.A. and M.M.) and Cancer Research UK (C.T. and A. Karpathakis).",

year = "2013",

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doi = "10.1038/ng.2821",

language = "English (US)",

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T1 - Somatic mutation of CDKN1B in small intestine neuroendocrine tumors

AU - Francis, Joshua M.

AU - Kiezun, Adam

AU - Ramos, Alex H.

AU - Serra, Stefano

AU - Pedamallu, Chandra Sekhar

AU - Qian, Zhi Rong

AU - Banck, Michaela S.

AU - Kanwar, Rahul

AU - Kulkarni, Amit A.

AU - Karpathakis, Anna

AU - Manzo, Veronica

AU - Contractor, Tanupriya

AU - Philips, Juliet

AU - Nickerson, Elizabeth

AU - Pho, Nam

AU - Hooshmand, Susanne M.

AU - Brais, Lauren K.

AU - Lawrence, Michael S.

AU - Pugh, Trevor

AU - McKenna, Aaron

AU - Sivachenko, Andrey

AU - Cibulskis, Kristian

AU - Carter, Scott L.

AU - Ojesina, Akinyemi I.

AU - Freeman, Samuel

AU - Jones, Robert T.

AU - Voet, Douglas

AU - Saksena, Gordon

AU - Auclair, Daniel

AU - Onofrio, Robert

AU - Shefler, Erica

AU - Sougnez, Carrie

AU - Grimsby, Jonna

AU - Green, Lisa

AU - Lennon, Niall

AU - Meyer, Tim

AU - Caplin, Martyn

AU - Chung, Daniel C.

AU - Beutler, Andreas S.

AU - Ogino, Shuji

AU - Thirlwell, Christina

AU - Shivdasani, Ramesh

AU - Asa, Sylvia L.

AU - Harris, Chris R.

AU - Getz, Gad

AU - Kulke, Matthew

AU - Meyerson, Matthew

N1 - Funding Information: This work was supported by grants from the Caring for Carcinoid Foundation (S.L.A. and M.M.), the Raymond and Beverly Sackler Foundation for the Arts and Sciences (C.T., A. Karpathakis, S.L.A. and M.M.) and Cancer Research UK (C.T. and A. Karpathakis).

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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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DO - 10.1038/ng.2821

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C2 - 24185511

AN - SCOPUS:84888369188

SN - 1061-4036

VL - 45

SP - 1483

EP - 1486

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Somatic mutation of CDKN1B in small intestine neuroendocrine tumors

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