Dataset Information

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

ABSTRACT:

Background

SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer.

Methods

This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types.

Results

A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort.

Conclusion

We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

SUBMITTER: Zheng X

PROVIDER: S-EPMC10360270 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

Zheng Xiaobin X Lin Jing J Xiong Jiani J Guan Yanfang Y Lan Bin B Li Yi Y Gao Xuan X Fei Zhaodong Z Chen Lisha L Chen Lizhu L Chen Ling L Chen Gang G Guo Zengqing Z Yi Xin X Cao Weiguo W Ai Xinghao X Zhou Chengzhi C Li Xiaofeng X Zhao Jun J Yan Xiangtao X Yu Qitao Q Si Lu L Chen Yu Y Chen Chuanben C

BMC cancer 20230721 1

<h4>Background</h4>SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. ...[more]

PMID: 37479966

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Dataset Information

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

Background

Methods

Results

Conclusion

Publications

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

Similar Datasets

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