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Poster Discussion session - Translational research 1

4788 - Tumor mutational burden and prognosis across pan-cancers


20 Oct 2018


Poster Discussion session - Translational research 1


Translational Research

Tumour Site


Hao Ding


Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269


H. Ding1, J. Zhao2, Y. Zhang2, G. Wang2, S. Cai2, F. Qiu3

Author affiliations

  • 1 Department Of Respiratory Disease, Affiliated People's Hospital of Jiangsu University, 212002 - Zhenjiang/CN
  • 2 The Medical Department, Shanghai 3D Medicines.Inc, 201114 - Shanghai/CN
  • 3 Department Of Oncology, The First Affiliated Hospital of Nanchang University, 330006 - Nanchang/CN


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Abstract 4788


Tumor mutational burden (TMB) is associated with genome instability and immunogenicity, which has been reported to play an important role in predicting the efficacy of immune checkpoint inhibitors. However, the relationship of TMB and prognosis in solid tumors is not yet fully understood. In this study, we aimed to explore the association between TMB and prognosis across pan-cancers.


Whole-exome sequencing from 7882 solid tumors, spanning 22 cancer types from The Cancer Genome Atlas were analyzed. TMB was defined by total non-silent somatic mutation counts in coding region. Patients were classified into four groups based on the quartiles of TMB in each tumor. All Hazard ratios (HR) were reported as the risk ratio of the top 25% to the bottom 25% group.Table: 57PD

The associations of TMB and OS across pan-cancers

tumorfull namesTMB-median (interquartile)ALLStage I-IIStage III-IV
NHR(95% CI)PNHR(95% CI)PNHR(95% CI)P
BLCABladder Urothelial Carcinoma151(85-269)4080.51(0.33-0.78)<0.0011311.07(0.45-2.55)0.892750.41(0.24-0.68)<0.001
BRCABreast invasive carcinoma39(26-69)9701.48(0.87-2.54)0.157200.98(0.49-1.94)0.952294.46(1.57-12.69)<0.001
COADColon adenocarcinoma111(82-167)3781.43(0.79-2.58)0.242023.24(0.93-11.37)0.071651.57(0.7-3.5)0.27
ESCAEsophageal carcinoma100(77-144)1831.84(0.98-3.48)0.06973.01(1.18-7.68)0.02631.07(0.36-3.14)0.90
GBMGlioblastoma multiforme47(37-64)3851.01(0.73-1.42)0.93(-)(-)(-)(-)(-)(-)
HNSCHead and Neck squamous cell carcinoma92(60-140)5061.65(1.11-2.45)0.01963.94(1.34-11.59)0.013411.11(0.69-1.78)0.66
KIRCKidney renal clear cell carcinoma48(35-63)3333.72(1.79-7.75)<0.0012228.23(1.9-35.6)<0.0011091.82(0.75-4.38)0.18
KIRPKidney renal papillary cell carcinoma54(35-73)2770.39(0.13-1.15)0.091871.17(0.19-7.04)0.8663(-)(-)
LGGBrain Lower Grade Glioma25(18-34)5015.03(2.87-8.8)<0.001(-)(-)(-)(-)(-)(-)
LIHCLiver hepatocellular carcinoma77(55-107)3571.5(0.88-2.53)0.132501.87(0.87-3.98)0.11861.36(0.61-3.05)0.45
LUADLung adenocarcinoma171(74-338)5010.83(0.54-1.28)0.393900.89(0.52-1.52)0.671040.69(0.33-1.46)0.33
LUSCLung squamous cell carcinoma205(148-297)4830.75(0.52-1.09)0.133900.7(0.46-1.06)0.09890.92(0.38-2.21)0.84
OVOvarian serous cystadenocarcinoma79(53-130)4290.73(0.52-1.03)0.08(-)(-)(-)(-)(-)(-)
PAADPancreatic adenocarcinoma35(25-46)1731.62(0.88-3.02)0.12(-)(-)(-)(-)(-)(-)
READRectum adenocarcinoma95(74-127)1270.68(0.21-2.27)0.53611.22(0.11-13.47)0.87580.6(0.1-3.72)0.59
SKCMSkin Cutaneous Melanoma226(62-415)1030.45(0.15-1.3)0.14670.14(0.01-1.32)0.09311.51(0.36-6.32)0.58
STADStomach adenocarcinoma106(66-216)4090.52(0.34-0.8)<0.0011780.45(0.2-0.98)0.052140.53(0.31-0.92)0.02
THCAThyroid carcinoma9(6-13)4886.92(0.85-56.28)0.07325(-)(-)1611.34(0.16-11.19)0.79
UCECUterine Corpus Endometrial Carcinoma89(47-562)5270.27(0.13-0.57)<0.001(-)(-)(-)(-)(-)(-)
UVMUveal Melanoma12(9-15)682.5(0.45-13.88)0.2937(-)(-)302.4(0.19-30.98)0.50


Among 22 tumors, the level of TMB of top five tumors (median, interquartile, sample size) were: SKCM (226, 62-415, 103), LUSC (205, 148-297, 483), LUAD (171, 74-338, 501), BLCA (151, 85-269, 408), COAD (111, 82-167, 378). In all patient analyses of each tumor, higher TMB was associated with longer overall survival (OS) in BLCA, STAD and UCEC, and was associated with shorter OS in HNSC, KIRC and LGG. In stage I-II of each tumor, higher TMB was significantly associated with prolonged OS in STAD, but with shorter OS in ESCA, HNSC and KIRC. In stage III-IV of each tumor, higher TMB was significantly associated with prolonged OS in BLCA and STAD, but with shorter OS in BRCA. In 5 tumors (including BLCA, HNSC, KIRC, LUSC and THCA), patients with higher pathological stage had significantly higher TMB (P < 0.05). However, only in COAD and READ, patients with higher stage had significantly lower TMB (P < 0.05).


Higher TMB played different roles in various tumors, which may be attribute to different driver mutations or other factors. Further analyses of underlying mechanism were underway to confirm and explore the potential prognosis prediction of TMB across pan-cancers.

Clinical trial identification

Legal entity responsible for the study

Feng Qiu.


Has not received any funding.

Editorial Acknowledgement


All authors have declared no conflicts of interest.

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