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
248P - Retrospective review of metastatic carcinoma of cervix from a tertiary cancer institute of south India
Presenter: Arkoprovo Halder
Session: Poster display session
Resources:
Abstract
249P - Accuracy of endometrial biopsy by Pipelle: A systematic review and meta-analysis
Presenter: Jinhai Gou
Session: Poster display session
Resources:
Abstract
250P - Non-endometrioid endometrial cancer: Analysis of different adjuvant treatment modalities
Presenter: Gonçalo Nogueira da Costa
Session: Poster display session
Resources:
Abstract
251P - A prognostic index model for predicting long-term recurrence of uterine leiomyoma after initial myomectomy in women aged 18-44 years
Presenter: Xiu Ming
Session: Poster display session
Resources:
Abstract
252P - Uterine sarcomas in Qatar: Clinico-pathological characteristics and treatment outcome
Presenter: Ashraf Fadlelseid
Session: Poster display session
Resources:
Abstract
253P - Anti-PD-1-induced reinvigoration of tumour-infiltrating CD8+ T cells in epithelial ovarian cancer patients is correlated with T cell factor-1
Presenter: Junsik Park
Session: Poster display session
Resources:
Abstract
254P - Cyclin E1 is a shared biomarker of subsets of high grade serous ovarian cancer (HGSOC) and basal like breast cancer (BLBC)
Presenter: Diar Aziz
Session: Poster display session
Resources:
Abstract
255P - MEX3A is a prognostic biomarker and correlates with RNA splicing and cell proliferation in endometrial cancer by analysis of RNA-seq data
Presenter: Huining Jing
Session: Poster display session
Resources:
Abstract
256P - Lnc-AL445665.1-4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
Presenter: E Yang
Session: Poster display session
Resources:
Abstract
257P - Treatment results of low risk gestational trophoblastic neoplasia (GTN) from a tertiary hospital, Chennai, India
Presenter: Rakesh M. P
Session: Poster display session
Resources:
Abstract