ArticleAnnals of translational medicine2021
Estimating tumor mutational burden across multiple cancer types using whole-exome sequencing.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis.Clinical and experimental medicine · 2024Pooled it
- Germline regulation of tumor evolutionary dynamics shapes multiple myeloma progression.bioRxiv : the preprint server for biology · 2026Article
- Machine learning-based models for tumor mutation burden prediction in gastrointestinal cancers: a systematic review and meta-analysis.Discover oncology · 2026Review
- Pooling multimodal cancer data across unaligned embedding spaces maintains tumor of origin signal.Bioinformatics advances · 2026Article
- Nonhypermutator Cancers Access Driver Mutations Through Reversals in Germline Mutational Bias.Molecular biology and evolution · 2025Article
- SHH Signaling as a Key Player in Endometrial Cancer: Unveiling the Correlation with Good Prognosis, Low Proliferation, and Anti-Tumor Immune Milieu.International journal of molecular sciences · 2024Article
- Recent Advances in Immunotherapy for Advanced Biliary Tract Cancer.Current treatment options in oncology · 2024Review
- A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Review
- Bias and inconsistency in the estimation of tumour mutation burden.BMC cancer · 2022Article
- Multi-target combinatory strategy to overcome tumor immune escape.Frontiers of medicine · 2022Review
- DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.Frontiers in oncology · 2022Article
- Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing.Frontiers in oncology · 2022Article
- Pathways to hypermutation in high-grade gliomas: Mechanisms, syndromes, and opportunities for immunotherapy.Neuro-oncology advancesReview
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9 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor mutational burden (TMB) is emerging as a promising biomarker in immune checkpoint inhibitor (ICI) therapy. Despite whole-exome sequencing (WES) being the gold standard for quantifying TMB, TMB is determined by selected targeted panels in most cases, and WES-derived TMB data are lacking due to the greater cost and complexity. Determining TMB thresholds is another issue that needs attention.
methodsA total of 309 patients who had received ICI therapy, representing five cancers (listed in "Results"), were recruited. Among them, 269 patients were evaluable for survival analysis. Tumor and matched blood samples from the patients were analyzed using WES and somatic mutations were determined. TMB is defined as the total number of somatic nonsynonymous mutations in the tumor exome in our study. The patients were divided into different TMB subgroups according to a common fixed number (10 mutations/Mb) or the top tertile within each tumor type.
resultsThe distribution of WES-derived median TMBs was highly variable across different tumor types, ranging from 2.71 (cholangiocarcinoma) to 2.97 (nervous system tumor), 3.69 (gastric cancer), 4.31 (hepatocellular carcinoma), and 4.64 [colorectal cancer (CRC)] mutations/Mb. In CRC, the survival benefit of TMB-high patients was significant using both the top tertile and the 10 mutations/Mb threshold. In hepatocellular carcinoma, the 10 mutations/Mb threshold showed an advantage over the top tertile threshold. Among patients with nervous system tumors, cholangiocarcinoma, and gastric cancer, no obvious survival differences were observed between the TMB-high and TMB-low groups with either TMB stratification approach.
conclusionsThe TMB threshold criterion may vary for different cancers. Our data suggest that TMB is unable to predict ICI benefit across all cancer types in Chinese patients. However, it may be an effective biomarker for predicting the clinical benefit of ICI therapy for patients with CRC.
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