Tumor mutation burden in Chinese cancer patients and the underlying driving pathways of high tumor mutation burden across different cancer types.
Chinese
Tumor mutation burden (TMB)
cancer-related gene panel
gene signature
Journal
Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
entrez:
15
8
2020
pubmed:
15
8
2020
medline:
15
8
2020
Statut:
ppublish
Résumé
Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction. Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping. TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer. TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.
Sections du résumé
BACKGROUND
BACKGROUND
Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction.
METHODS
METHODS
Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping.
RESULTS
RESULTS
TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer.
CONCLUSIONS
CONCLUSIONS
TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.
Identifiants
pubmed: 32793704
doi: 10.21037/atm-20-3807
pii: atm-08-14-860
pmc: PMC7396744
doi:
Types de publication
Journal Article
Langues
eng
Pagination
860Informations de copyright
2020 Annals of Translational Medicine. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3807). Dr. SC, Dr. YSZ, Dr. HHZ, Dr. JY and Dr. TH report that they are employees of Burning Rock Biotech. The other authors have no conflicts of interest to declare.
Références
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Lancet Oncol. 2006 Jun;7(6):499-507
pubmed: 16750500
J Mol Diagn. 2018 Mar;20(2):225-231
pubmed: 29277635
Genome Med. 2017 Apr 19;9(1):34
pubmed: 28420421
J Clin Oncol. 2006 May 10;24(14):2158-63
pubmed: 16682734
Trends Immunol. 2018 Jul;39(7):536-548
pubmed: 29751996
N Engl J Med. 2018 May 31;378(22):2093-2104
pubmed: 29658845
J Clin Oncol. 2010 Oct 20;28(30):4616-20
pubmed: 20855837
Sci Transl Med. 2017 Jun 7;9(393):
pubmed: 28592566
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Cancer Cell. 2018 May 14;33(5):853-861.e4
pubmed: 29731394
Mol Cancer Ther. 2017 Nov;16(11):2598-2608
pubmed: 28835386
Cell. 2018 Jun 14;173(7):1770-1782.e14
pubmed: 29906450
J Clin Oncol. 2016 Jun 20;34(18):2141-7
pubmed: 27022117
Bioinformatics. 2004 Oct 12;20(15):2479-81
pubmed: 15073010
PLoS One. 2014 Mar 19;9(3):e91983
pubmed: 24647545
Gastroenterology. 2017 Jan;152(1):68-74.e2
pubmed: 27856273
Nature. 2018 Jan 18;553(7688):347-350
pubmed: 29320474
BMC Med. 2016 Oct 25;14(1):168
pubmed: 27776519
Nat Commun. 2017 Apr 25;8:15102
pubmed: 28440315
JAMA Oncol. 2019 Apr 1;5(4):471-478
pubmed: 30589920
J Cancer. 2018 Jun 6;9(13):2302-2307
pubmed: 30026825
Transl Lung Cancer Res. 2019 Aug;8(4):553-555
pubmed: 31555531
Nat Rev Clin Oncol. 2015 Jun;12(6):319-34
pubmed: 25824606
Nature. 2012 Sep 27;489(7417):519-25
pubmed: 22960745
J Thorac Oncol. 2017 Apr;12(4):663-672
pubmed: 28007624
J Clin Oncol. 2018 Mar 1;36(7):633-641
pubmed: 29337640
J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
pubmed: 15741570
Clin Cancer Res. 2014 Dec 15;20(24):6605-17
pubmed: 25316812