| Autor: |
Danyi Wang, Brian Elenbaas, Karthikeyan Murugesan, Kunal Shah, Meagan Montesion, Ioannis Gounaris, Juergen Scheuenpflug, Giuseppe Locatelli, Zheng Feng |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
npj Precision Oncology, Vol 7, Iss 1, Pp 1-14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2397-768X |
| DOI: |
10.1038/s41698-023-00442-4 |
| Popis: |
Abstract The DNA damage response (DDR) pathway regulates DNA repair and cell survival, and inactivating mutations in DDR genes can increase tumour mutational burden (TMB), a predictive biomarker of treatment benefit from anti-PD-1/PD-L1 immunotherapies. However, a better understanding of the relationship among specific DDR mutations, TMB and PD-L1 expression is needed to improve translational strategies. Here, we determined genomic alteration frequencies in selected DDR genes that are clinically actionable biomarkers and investigated their association with TMB and PD-L1 in bladder, colorectal, non-small cell lung, ovarian and prostate cancers using the FoundationInsights® web portal. Our results not only confirm known associations, such as mismatch repair and POLE gene mutations with high TMB, but also identify significant associations between mutations in the SWI/SNF chromatin remodelling genes ARID1A and SMARCA4 and high TMB in multiple tumour types. Mutations in the ATR gene were associated with high TMB in colorectal and prostate cancers; however, associations between individual DDR mutations and high PD-L1 expression were uncommon and tumour-type specific. Finally, we found that high TMB and high PD-L1 expression were poorly associated, emphasising their independence as predictive biomarkers for immune checkpoint inhibitor use. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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