Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients Journal Article


Authors: Zehir, A.; Benayed, R.; Shah, R. H.; Syed, A.; Middha, S.; Kim, H. R.; Srinivasan, P.; Gao, J.; Chakravarty, D.; Devlin, S. M.; Hellmann, M. D.; Barron, D. A.; Schram, A. M.; Hameed, M.; Dogan, S.; Ross, D. S.; Hechtman, J. F.; DeLair, D. F.; Yao, J.; Mandelker, D. L.; Cheng, D. T.; Chandramohan, R.; Mohanty, A. S.; Ptashkin, R. N.; Jayakumaran, G.; Prasad, M.; Syed, M. H.; Rema, A. B.; Liu, Z. Y.; Nafa, K.; Borsu, L.; Sadowska, J.; Casanova, J.; Bacares, R.; Kiecka, I. J.; Razumova, A.; Son, J. B.; Stewart, L.; Baldi, T.; Mullaney, K. A.; Al-Ahmadie, H.; Vakiani, E.; Abeshouse, A. A.; Penson, A. V.; Jonsson, P.; Camacho, N.; Chang, M. T.; Won, H. H.; Gross, B. E.; Kundra, R.; Heins, Z. J.; Chen, H. W.; Phillips, S.; Zhang, H.; Wang, J.; Ochoa, A.; Wills, J.; Eubank, M.; Thomas, S. B.; Gardos, S. M.; Reales, D. N.; Galle, J.; Durany, R.; Cambria, R.; Abida, W.; Cercek, A.; Feldman, D. R.; Gounder, M. M.; Hakimi, A. A.; Harding, J. J.; Iyer, G.; Janjigian, Y. Y.; Jordan, E. J.; Kelly, C. M.; Lowery, M. A.; Morris, L. G. T.; Omuro, A. M.; Raj, N.; Razavi, P.; Shoushtari, A. N.; Shukla, N.; Soumerai, T. E.; Varghese, A. M.; Yaeger, R.; Coleman, J.; Bochner, B.; Riely, G. J.; Saltz, L. B.; Scher, H. I.; Sabbatini, P. J.; Robson, M. E.; Klimstra, D. S.; Taylor, B. S.; Baselga, J.; Schultz, N.; Hyman, D. M.; Arcila, M. E.; Solit, D. B.; Ladanyi, M.; Berger, M. F.
Article Title: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Abstract: Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Journal Title: Nature Medicine
Volume: 23
Issue: 6
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2017-06-01
Start Page: 703
End Page: 713
Language: English
DOI: 10.1038/nm.4333
PROVIDER: scopus
PMCID: PMC5461196
PUBMED: 28481359
DOI/URL:
Notes: Erratum issued, see DOI: 10.1038/nm0817-1004c -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    253 Coleman
  2. Meera Hameed
    195 Hameed
  3. Leonard B Saltz
    702 Saltz
  4. Khedoudja Nafa
    213 Nafa
  5. Mark E Robson
    531 Robson
  6. David Solit
    617 Solit
  7. James Joseph Harding
    139 Harding
  8. Paul J Sabbatini
    237 Sabbatini
  9. Antonio Marcilio Padula Omuro
    196 Omuro
  10. Darren Richard Feldman
    250 Feldman
  11. Jinjuan Yao
    38 Yao
  12. Yelena Yuriy Janjigian
    228 Janjigian
  13. David S Klimstra
    943 Klimstra
  14. Marc Ladanyi
    1124 Ladanyi
  15. Maeve Aine Lowery
    132 Lowery
  16. Gopakumar Vasudeva Iyer
    205 Iyer
  17. Gregory J Riely
    458 Riely
  18. Mrinal M Gounder
    138 Gounder
  19. Rona Denit Yaeger
    157 Yaeger
  20. David Hyman
    345 Hyman
  21. Luc Morris
    179 Morris
  22. Snjezana Dogan
    135 Dogan
  23. Bernard Bochner
    388 Bochner
  24. Ahmet Zehir
    267 Zehir
  25. Michael Forman Berger
    557 Berger
  26. Maria Eugenia Arcila
    516 Arcila
  27. Efsevia Vakiani
    204 Vakiani
  28. Howard Scher
    1033 Scher
  29. Neerav Shukla
    103 Shukla
  30. Deborah F DeLair
    103 DeLair
  31. Jianjiong Gao
    92 Gao
  32. Wassim Abida
    100 Abida
  33. Dara Stacy Ross
    79 Ross
  34. Matthew David Hellmann
    326 Hellmann
  35. Barry Stephen Taylor
    222 Taylor
  36. Nikolaus D Schultz
    308 Schultz
  37. Benjamin E Gross
    33 Gross
  38. Alison Michele Schram
    64 Schram
  39. Helen Hyeong-Eun Won
    97 Won
  40. Sean McCarthy Devlin
    433 Devlin
  41. Ruben Bacares
    16 Bacares
  42. Abraham Ari Hakimi
    229 Hakimi
  43. Stuart M Gardos
    18 Gardos
  44. Hsiao-Wei Chen
    20 Chen
  45. Ronak Hasmukh Shah
    50 Shah
  46. Donavan Tai Suan Cheng
    51 Cheng
  47. Jose T Baselga
    480 Baselga
  48. Aijazuddin Syed
    33 Syed
  49. Jaclyn Frances Hechtman
    189 Hechtman
  50. Nitya Prabhakar Raj
    57 Raj
  51. Pedram Razavi
    99 Razavi
  52. Rym Benayed
    143 Benayed
  53. Matthew   Chang
    27 Chang
  54. David   Barron
    11 Barron
  55. Meera   Prasad
    12 Prasad
  56. Zhen Yu   Liu
    3 Liu
  57. Julie Bun Son
    4 Son
  58. Tessara   Baldi
    11 Baldi
  59. Abhinita Subhadarshin Mohanty
    23 Mohanty
  60. Emmet John Jordan
    46 Jordan
  61. Jonathan   Wills
    22 Wills
  62. Stacy Bridget Thomas
    6 Thomas
  63. Sumit   Middha
    80 Middha
  64. Jesse   Galle
    8 Galle
  65. Mustafa H Syed
    21 Syed
  66. Karl Philip Jonsson
    47 Jonsson
  67. Alexander Vincent Penson
    39 Penson
  68. Ciara Marie Kelly
    36 Kelly
  69. Iwona J Kiecka
    5 Kiecka
  70. Michael   Eubank
    4 Eubank
  71. Zachary Joseph Heins
    11 Heins
  72. Ritika   Kundra
    40 Kundra
  73. Hongxin Zhang
    18 Zhang
  74. Hyunjae Ryan Kim
    7 Kim
  75. Dalicia Nicole Reales
    8 Reales
  76. Jiaojiao Wang
    3 Wang
  77. Robert Eugene Durany
    3 Durany
  78. Angelica Ochoa
    12 Ochoa