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
    343 Coleman
  2. Meera Hameed
    281 Hameed
  3. Leonard B Saltz
    791 Saltz
  4. Khedoudja Nafa
    243 Nafa
  5. Mark E Robson
    676 Robson
  6. David Solit
    779 Solit
  7. James Joseph Harding
    250 Harding
  8. Paul J Sabbatini
    262 Sabbatini
  9. Anna Mary Varghese
    145 Varghese
  10. Antonio Marcilio Padula Omuro
    204 Omuro
  11. Darren Richard Feldman
    341 Feldman
  12. Jinjuan Yao
    59 Yao
  13. Yelena Yuriy Janjigian
    395 Janjigian
  14. David S Klimstra
    978 Klimstra
  15. Marc Ladanyi
    1328 Ladanyi
  16. Maeve Aine Lowery
    133 Lowery
  17. Gopakumar Vasudeva Iyer
    344 Iyer
  18. Gregory J Riely
    599 Riely
  19. Mrinal M Gounder
    229 Gounder
  20. Rona Denit Yaeger
    316 Yaeger
  21. David Hyman
    354 Hyman
  22. Luc Morris
    279 Morris
  23. Snjezana Dogan
    187 Dogan
  24. Bernard Bochner
    468 Bochner
  25. Ahmet Zehir
    343 Zehir
  26. Michael Forman Berger
    765 Berger
  27. Maria Eugenia Arcila
    657 Arcila
  28. Efsevia Vakiani
    264 Vakiani
  29. Howard Scher
    1130 Scher
  30. Neerav Shukla
    159 Shukla
  31. Deborah F DeLair
    106 DeLair
  32. Jianjiong Gao
    132 Gao
  33. Wassim Abida
    156 Abida
  34. Dara Stacy Ross
    144 Ross
  35. Matthew David Hellmann
    411 Hellmann
  36. Barry Stephen Taylor
    238 Taylor
  37. Nikolaus D Schultz
    487 Schultz
  38. Benjamin E Gross
    44 Gross
  39. Alison Michele Schram
    123 Schram
  40. Helen Hyeong-Eun Won
    109 Won
  41. Sean McCarthy Devlin
    601 Devlin
  42. Ruben Bacares
    18 Bacares
  43. Abraham Ari Hakimi
    324 Hakimi
  44. Stuart M Gardos
    21 Gardos
  45. Hsiao-Wei Chen
    30 Chen
  46. Ronak Hasmukh Shah
    72 Shah
  47. Donavan Tai Suan Cheng
    52 Cheng
  48. Jose T Baselga
    484 Baselga
  49. Aijazuddin Syed
    52 Syed
  50. Jaclyn Frances Hechtman
    212 Hechtman
  51. Nitya Prabhakar Raj
    106 Raj
  52. Pedram Razavi
    172 Razavi
  53. Rym Benayed
    188 Benayed
  54. Matthew   Chang
    29 Chang
  55. David   Barron
    11 Barron
  56. Meera   Prasad
    13 Prasad
  57. Zhen Yu   Liu
    3 Liu
  58. Tessara   Baldi
    14 Baldi
  59. Abhinita Subhadarshin Mohanty
    39 Mohanty
  60. Emmet John Jordan
    47 Jordan
  61. Jonathan   Wills
    24 Wills
  62. Stacy Bridget Thomas
    6 Thomas
  63. Sumit   Middha
    83 Middha
  64. Jesse   Galle
    17 Galle
  65. Mustafa H Syed
    23 Syed
  66. Karl Philip Jonsson
    50 Jonsson
  67. Alexander Vincent Penson
    54 Penson
  68. Ciara Marie Kelly
    90 Kelly
  69. Iwona J Kiecka
    7 Kiecka
  70. Diana Lauren Mandelker
    178 Mandelker
  71. Michael   Eubank
    5 Eubank
  72. Zachary Joseph Heins
    22 Heins
  73. Ritika   Kundra
    89 Kundra
  74. Hongxin Zhang
    47 Zhang
  75. Hyunjae Ryan Kim
    7 Kim
  76. Dalicia Nicole Reales
    10 Reales
  77. Jiaojiao Wang
    3 Wang
  78. Robert Eugene Durany
    3 Durany
  79. Angelica Ochoa
    30 Ochoa