Abstract 370P
Background
In this study, we examined the TMB landscape of 5,660 pan-cancer cases in Chinese population, using NGS panel. We established cancer-specific and histology-specific biological pathways associated with the TMB status. In addition, as a proof on concept, an unsupervised algorithm was conducted using stepwise logistic regression to generate TMB-predicting signatures from both lung adenocarcinoma and lung squamous cell carcinoma.
Methods
Patients: 5,660 Chinese cancer patients across 11 cancer types Panel: Targeted sequencing was performed on tissue samples using a panel consisting of 295 or 520 cancer-related genes, spanning 1.4 and 1.6Mb of human genome, respectively. An average sequencing depth of 1,000X and 10,000x were achieved for tissue and plasma samples, respectively. Tumor mutation burden: calculated as the ratio of mutation count to the size of coding region of the panel, excluding CNV, fusions, large genomic rearrangements and mutations occurring on the kinase domain of EGFR and ALK.
Results
Across the 11 cancer types included in the analysis, lung squamous cell carcinoma had the highest average TMB, whereas sarcoma has the lowest TMB. High microsatellite instability, DNA damage response deficiency, and homologous recombination repair deficiency indicated significantly higher TMB.The independent predictive power for TMB 26 biological pathways was tested in 11 cancer types. Mismatch repair, DNA damage response, homologous recombination repair, and PI3K-AKT signaling pathway were most commonly correlated with high-TMB. In contrast, ERBB signaling pathway, and adhesion-related pathways were most commonly correlated with low-TMB. Moreover, we developed a 23- and 16-gene signature for TMB prediction for LUAD and LUSC, respectively, with 12 genes shared by both signatures, indicating a histology- specific mechanism for driving high- TMB in lung cancer.
Conclusions
The findings extended 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Burning Rock Biotech.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
508P - Efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib in first-line treatment for advanced lung squamous carcinoma: A phase II study
Presenter: Jinliang Wang
Session: Poster display session
Resources:
Abstract
525P - Retrospective analysis of outcomes of cisplatin and irinotecan combination chemotherapy for unresectable thymic carcinoma
Presenter: Akito Fukuda
Session: Poster display session
Resources:
Abstract
524P - A study in recurrent small cell lung cancer patients, comparing weekly paclitaxel, irinotecan and temozolomide in second-line: A prospective study from a south Indian tertiary cancer hospital
Presenter: LALATENDU MOHARANA
Session: Poster display session
Resources:
Abstract
505P - PD-L1 expression in ALK rearranged NSCLC: All questions answered?
Presenter: Amrith B P
Session: Poster display session
Resources:
Abstract
487P - Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma
Presenter: Chee Shee Chai
Session: Poster display session
Resources:
Abstract
492P - Feasibility of rebiopsy and sequential treatment of EGFR tyrosine kinase inhibitors in real world patients with EGFR mutant non-small cell lung cancer
Presenter: Heekyung Ahn
Session: Poster display session
Resources:
Abstract
513P - Phase II study of vitamin B12 and folate supplementation for patients undergoing chemotherapy with pemetrexed
Presenter: Shingo Kitagawa
Session: Poster display session
Resources:
Abstract
493P - Is exon 19 deletion different from exon 21 mutation in advanced non-small cell lung cancer: A single centre experience
Presenter: Sarita Shrivastva
Session: Poster display session
Resources:
Abstract
494P - Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib
Presenter: Chee Shee Chai
Session: Poster display session
Resources:
Abstract
517P - High BRCA1 expression is independently correlated with decreased overall survival in lung adenocarcinoma: Evidence from meta and bioinformatics analyses
Presenter: Fengzhu Guo
Session: Poster display session
Resources:
Abstract