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
    314 Coleman
  2. Meera Hameed
    247 Hameed
  3. Leonard B Saltz
    760 Saltz
  4. Khedoudja Nafa
    236 Nafa
  5. Mark E Robson
    644 Robson
  6. David Solit
    729 Solit
  7. James Joseph Harding
    208 Harding
  8. Paul J Sabbatini
    258 Sabbatini
  9. Anna Mary Varghese
    126 Varghese
  10. Antonio Marcilio Padula Omuro
    204 Omuro
  11. Darren Richard Feldman
    310 Feldman
  12. Jinjuan Yao
    54 Yao
  13. Yelena Yuriy Janjigian
    349 Janjigian
  14. David S Klimstra
    976 Klimstra
  15. Marc Ladanyi
    1277 Ladanyi
  16. Maeve Aine Lowery
    133 Lowery
  17. Gopakumar Vasudeva Iyer
    288 Iyer
  18. Gregory J Riely
    571 Riely
  19. Mrinal M Gounder
    207 Gounder
  20. Rona Denit Yaeger
    263 Yaeger
  21. David Hyman
    352 Hyman
  22. Luc Morris
    248 Morris
  23. Snjezana Dogan
    173 Dogan
  24. Bernard Bochner
    444 Bochner
  25. Ahmet Zehir
    336 Zehir
  26. Michael Forman Berger
    701 Berger
  27. Maria Eugenia Arcila
    618 Arcila
  28. Efsevia Vakiani
    242 Vakiani
  29. Howard Scher
    1110 Scher
  30. Neerav Shukla
    140 Shukla
  31. Deborah F DeLair
    105 DeLair
  32. Jianjiong Gao
    129 Gao
  33. Wassim Abida
    141 Abida
  34. Dara Stacy Ross
    116 Ross
  35. Matthew David Hellmann
    405 Hellmann
  36. Barry Stephen Taylor
    236 Taylor
  37. Nikolaus D Schultz
    429 Schultz
  38. Benjamin E Gross
    43 Gross
  39. Alison Michele Schram
    102 Schram
  40. Helen Hyeong-Eun Won
    109 Won
  41. Sean McCarthy Devlin
    553 Devlin
  42. Ruben Bacares
    17 Bacares
  43. Abraham Ari Hakimi
    295 Hakimi
  44. Stuart M Gardos
    21 Gardos
  45. Hsiao-Wei Chen
    30 Chen
  46. Ronak Hasmukh Shah
    62 Shah
  47. Donavan Tai Suan Cheng
    52 Cheng
  48. Jose T Baselga
    483 Baselga
  49. Aijazuddin Syed
    45 Syed
  50. Jaclyn Frances Hechtman
    208 Hechtman
  51. Nitya Prabhakar Raj
    94 Raj
  52. Pedram Razavi
    142 Razavi
  53. Rym Benayed
    184 Benayed
  54. Matthew   Chang
    28 Chang
  55. David   Barron
    11 Barron
  56. Meera   Prasad
    13 Prasad
  57. Zhen Yu   Liu
    3 Liu
  58. Tessara   Baldi
    13 Baldi
  59. Abhinita Subhadarshin Mohanty
    35 Mohanty
  60. Emmet John Jordan
    47 Jordan
  61. Jonathan   Wills
    23 Wills
  62. Stacy Bridget Thomas
    6 Thomas
  63. Sumit   Middha
    82 Middha
  64. Jesse   Galle
    16 Galle
  65. Mustafa H Syed
    23 Syed
  66. Karl Philip Jonsson
    50 Jonsson
  67. Alexander Vincent Penson
    53 Penson
  68. Ciara Marie Kelly
    76 Kelly
  69. Iwona J Kiecka
    6 Kiecka
  70. Diana Lauren Mandelker
    153 Mandelker
  71. Michael   Eubank
    4 Eubank
  72. Zachary Joseph Heins
    22 Heins
  73. Ritika   Kundra
    76 Kundra
  74. Hongxin Zhang
    43 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