High-throughput oncogene mutation profiling in human cancer

Roman K. Thomas; Alissa C. Baker; Ralph M. DeBiasi; Wendy Winckler; Thomas LaFramboise; William M. Lin; Meng Wang; Whei Feng; Thomas Zander; Laura E. MacConnaill; Jeffrey C. Lee; Rick Nicoletti; Charlie Hatton; Mary Goyette; Luc Girard; Kuntal Majmudar; Liuda Ziaugra; Kwok Kin Wong; Stacey Gabriel; Rameen Beroukhim; Michael Peyton; Jordi Barretina; Amit Dutt; Caroline Emery; Heidi Greulich; Kinjal Shah; Hidefumi Sasaki; Adi Gazdar; John Minna; Scott A. Armstrong; Ingo K. Mellinghoff; F. Stephen Hodi; Glenn Dranoff; Paul S. Mischel; Tim F. Cloughesy; Stan F. Nelson; Linda M. Liau; Kirsten Mertz; Mark A. Rubin; Holger Moch; Massimo Loda; William Catalona; Jonathan Fletcher; Sabina Signoretti; Frederic Kaye; Kenneth C. Anderson; George D. Demetri; Reinhard Dummer; Stephan Wagner; Meenhard Herlyn; William R. Sellers; Matthew Meyerson; Levi A. Garraway

doi:10.1038/ng1975

High-throughput oncogene mutation profiling in human cancer

Roman K. Thomas, Alissa C. Baker, Ralph M. DeBiasi, Wendy Winckler, Thomas LaFramboise, William M. Lin, Meng Wang, Whei Feng, Thomas Zander, Laura E. MacConnaill, Jeffrey C. Lee, Rick Nicoletti, Charlie Hatton, Mary Goyette, Luc Girard, Kuntal Majmudar, Liuda Ziaugra, Kwok Kin Wong, Stacey Gabriel, Rameen BeroukhimMichael Peyton, Jordi Barretina, Amit Dutt, Caroline Emery, Heidi Greulich, Kinjal Shah, Hidefumi Sasaki, Adi Gazdar, John Minna, Scott A. Armstrong, Ingo K. Mellinghoff, F. Stephen Hodi, Glenn Dranoff, Paul S. Mischel, Tim F. Cloughesy, Stan F. Nelson, Linda M. Liau, Kirsten Mertz, Mark A. Rubin, Holger Moch, Massimo Loda, William Catalona, Jonathan Fletcher, Sabina Signoretti, Frederic Kaye, Kenneth C. Anderson, George D. Demetri, Reinhard Dummer, Stephan Wagner, Meenhard Herlyn, William R. Sellers, Matthew Meyerson, Levi A. Garraway^*

^*Corresponding author for this work

Urology

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

905 Scopus citations

Abstract

Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.

Original language	English (US)
Pages (from-to)	347-351
Number of pages	5
Journal	Nature Genetics
Volume	39
Issue number	3
DOIs	https://doi.org/10.1038/ng1975
State	Published - Mar 2007

Funding

Perelman Fund for Cancer Research at Dana-Farber. I.K.M. and P.S.M. are supported by Accelerate Brain Tumor Cure. I.K.M., L.M.L, T.F.C., and P.S.M. are supported by the Henry E. Singleton Brain Tumor Program. I.K.M., L.M.L, T.F.C., S.F.N., M.M., W.R.S. and P.S.M. are supported by the Brain Tumor Funders’ Collaborative. M.M. and L.A.G. are supported by a grant from Genentech, Inc. M.M. is supported by the American Cancer Society. L.A.G is supported by the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation and the Novartis Institute for Biomedical Research. We thank E. Lander and G. Getz for comments and advice. R.K.T. is a Mildred-Scheel fellow of the Deutsche Krebshilfe. R.K.T. is supported by the International Association for the Study of Lung Cancer (IASLC). R.M.D. is supported by the Swiss national science foundation (no: 3100A0-103671/1). A.G and J.M. are supported by the National Cancer Institute through SPORE grant P50CA70907. G.D.D. is supported by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Quick Family Fund for Cancer Research and the Ronald O.

ASJC Scopus subject areas

Genetics

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10.1038/ng1975

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Thomas, R. K., Baker, A. C., DeBiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConnaill, L. E., Lee, J. C., Nicoletti, R., Hatton, C., Goyette, M., Girard, L., Majmudar, K., Ziaugra, L., Wong, K. K., Gabriel, S., ... Garraway, L. A. (2007). High-throughput oncogene mutation profiling in human cancer. Nature Genetics, 39(3), 347-351. https://doi.org/10.1038/ng1975

@article{bd09f4a128da42e48f1190a0c5a31a3e,

title = "High-throughput oncogene mutation profiling in human cancer",

abstract = "Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.",

author = "Thomas, {Roman K.} and Baker, {Alissa C.} and DeBiasi, {Ralph M.} and Wendy Winckler and Thomas LaFramboise and Lin, {William M.} and Meng Wang and Whei Feng and Thomas Zander and MacConnaill, {Laura E.} and Lee, {Jeffrey C.} and Rick Nicoletti and Charlie Hatton and Mary Goyette and Luc Girard and Kuntal Majmudar and Liuda Ziaugra and Wong, {Kwok Kin} and Stacey Gabriel and Rameen Beroukhim and Michael Peyton and Jordi Barretina and Amit Dutt and Caroline Emery and Heidi Greulich and Kinjal Shah and Hidefumi Sasaki and Adi Gazdar and John Minna and Armstrong, {Scott A.} and Mellinghoff, {Ingo K.} and Hodi, {F. Stephen} and Glenn Dranoff and Mischel, {Paul S.} and Cloughesy, {Tim F.} and Nelson, {Stan F.} and Liau, {Linda M.} and Kirsten Mertz and Rubin, {Mark A.} and Holger Moch and Massimo Loda and William Catalona and Jonathan Fletcher and Sabina Signoretti and Frederic Kaye and Anderson, {Kenneth C.} and Demetri, {George D.} and Reinhard Dummer and Stephan Wagner and Meenhard Herlyn and Sellers, {William R.} and Matthew Meyerson and Garraway, {Levi A.}",

note = "Funding Information: Perelman Fund for Cancer Research at Dana-Farber. I.K.M. and P.S.M. are supported by Accelerate Brain Tumor Cure. I.K.M., L.M.L, T.F.C., and P.S.M. are supported by the Henry E. Singleton Brain Tumor Program. I.K.M., L.M.L, T.F.C., S.F.N., M.M., W.R.S. and P.S.M. are supported by the Brain Tumor Funders{\textquoteright} Collaborative. M.M. and L.A.G. are supported by a grant from Genentech, Inc. M.M. is supported by the American Cancer Society. L.A.G is supported by the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation and the Novartis Institute for Biomedical Research. Funding Information: We thank E. Lander and G. Getz for comments and advice. R.K.T. is a Mildred-Scheel fellow of the Deutsche Krebshilfe. R.K.T. is supported by the International Association for the Study of Lung Cancer (IASLC). R.M.D. is supported by the Swiss national science foundation (no: 3100A0-103671/1). A.G and J.M. are supported by the National Cancer Institute through SPORE grant P50CA70907. G.D.D. is supported by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Quick Family Fund for Cancer Research and the Ronald O.",

year = "2007",

month = mar,

doi = "10.1038/ng1975",

language = "English (US)",

volume = "39",

pages = "347--351",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

Thomas, RK, Baker, AC, DeBiasi, RM, Winckler, W, LaFramboise, T, Lin, WM, Wang, M, Feng, W, Zander, T, MacConnaill, LE, Lee, JC, Nicoletti, R, Hatton, C, Goyette, M, Girard, L, Majmudar, K, Ziaugra, L, Wong, KK, Gabriel, S, Beroukhim, R, Peyton, M, Barretina, J, Dutt, A, Emery, C, Greulich, H, Shah, K, Sasaki, H, Gazdar, A, Minna, J, Armstrong, SA, Mellinghoff, IK, Hodi, FS, Dranoff, G, Mischel, PS, Cloughesy, TF, Nelson, SF, Liau, LM, Mertz, K, Rubin, MA, Moch, H, Loda, M, Catalona, W, Fletcher, J, Signoretti, S, Kaye, F, Anderson, KC, Demetri, GD, Dummer, R, Wagner, S, Herlyn, M, Sellers, WR, Meyerson, M & Garraway, LA 2007, 'High-throughput oncogene mutation profiling in human cancer', Nature Genetics, vol. 39, no. 3, pp. 347-351. https://doi.org/10.1038/ng1975

TY - JOUR

T1 - High-throughput oncogene mutation profiling in human cancer

AU - Thomas, Roman K.

AU - Baker, Alissa C.

AU - DeBiasi, Ralph M.

AU - Winckler, Wendy

AU - LaFramboise, Thomas

AU - Lin, William M.

AU - Wang, Meng

AU - Feng, Whei

AU - Zander, Thomas

AU - MacConnaill, Laura E.

AU - Lee, Jeffrey C.

AU - Nicoletti, Rick

AU - Hatton, Charlie

AU - Goyette, Mary

AU - Girard, Luc

AU - Majmudar, Kuntal

AU - Ziaugra, Liuda

AU - Wong, Kwok Kin

AU - Gabriel, Stacey

AU - Beroukhim, Rameen

AU - Peyton, Michael

AU - Barretina, Jordi

AU - Dutt, Amit

AU - Emery, Caroline

AU - Greulich, Heidi

AU - Shah, Kinjal

AU - Sasaki, Hidefumi

AU - Gazdar, Adi

AU - Minna, John

AU - Armstrong, Scott A.

AU - Mellinghoff, Ingo K.

AU - Hodi, F. Stephen

AU - Dranoff, Glenn

AU - Mischel, Paul S.

AU - Cloughesy, Tim F.

AU - Nelson, Stan F.

AU - Liau, Linda M.

AU - Mertz, Kirsten

AU - Rubin, Mark A.

AU - Moch, Holger

AU - Loda, Massimo

AU - Catalona, William

AU - Fletcher, Jonathan

AU - Signoretti, Sabina

AU - Kaye, Frederic

AU - Anderson, Kenneth C.

AU - Demetri, George D.

AU - Dummer, Reinhard

AU - Wagner, Stephan

AU - Herlyn, Meenhard

AU - Sellers, William R.

AU - Meyerson, Matthew

AU - Garraway, Levi A.

N1 - Funding Information: Perelman Fund for Cancer Research at Dana-Farber. I.K.M. and P.S.M. are supported by Accelerate Brain Tumor Cure. I.K.M., L.M.L, T.F.C., and P.S.M. are supported by the Henry E. Singleton Brain Tumor Program. I.K.M., L.M.L, T.F.C., S.F.N., M.M., W.R.S. and P.S.M. are supported by the Brain Tumor Funders’ Collaborative. M.M. and L.A.G. are supported by a grant from Genentech, Inc. M.M. is supported by the American Cancer Society. L.A.G is supported by the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation and the Novartis Institute for Biomedical Research. Funding Information: We thank E. Lander and G. Getz for comments and advice. R.K.T. is a Mildred-Scheel fellow of the Deutsche Krebshilfe. R.K.T. is supported by the International Association for the Study of Lung Cancer (IASLC). R.M.D. is supported by the Swiss national science foundation (no: 3100A0-103671/1). A.G and J.M. are supported by the National Cancer Institute through SPORE grant P50CA70907. G.D.D. is supported by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Quick Family Fund for Cancer Research and the Ronald O.

PY - 2007/3

Y1 - 2007/3

N2 - Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.

AB - Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.

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DO - 10.1038/ng1975

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JF - Nature Genetics

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ER -

High-throughput oncogene mutation profiling in human cancer

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