Abstract 2314
Background
Immune checkpoint inhibitors (ICIs) elicits durable responses in non–small cell lung cancer (NSCLC), but only a fraction of patients responded. TP53 and ATM co-mutation may lead to genomic instability and hypermutation. However, the prevalence and utility of a TP53/ATM co-mutation as a biomarker to ICIs are not fully understood.
Methods
This was a multiple cohort pooled study, 2020 NSCLC samples from Geneplus Institute, 1031 samples from TCGA, 1567 samples from MSKCC, 853 samples from POLAR/OAK databases were statically analyzed. Next-generation sequencing assays were performed in the Geneplus Institute. Genomic, transcriptomic and clinical data were obtained from the TCGA, MSKCC, POLAR/OAK databases. Comprehensive profiling was performed to determine the prevalence of TP53/ATM co-mutation and correlation with the prognosis and the response to ICIs.
Results
TP53/ATM co-mutation sites were found to be scattered throughout the genes and we did not observe any significant difference in TP53/ATM co-mutated frequency within the histologic subtypes and driver genes. In five independent NSCLC cohorts, TP53/ATM co-mutation contributed to significantly higher tumor mutation burden (TMB) compared to both the sole mutation and both wild type groups. Furthermore, in the MSKCC-IO cohort, a TP53/ATM co-mutation was associated with better OS than sole mutation and both wild type groups, especially in pan-cancer (P=.241, NSCLC and P<.0001, Pan-cancer). Similar results were shown in the POLAR/OAK cohort, the disease control benefit rate, and progression free survival (PFS) and OS were all greater in patients with the TP53/ATM co-mutation compared with the other three groups. GSEA showed that IFN-α response, IFN-γ response, IL6/JAK/STAT3 signaling, and TNF-α signaling pathways had higher levels of activation and there was greater PD-L1 expression in the co-mutated group, compared with solely mutated and both wild type group.
Conclusions
Our findings suggest that patients with TP53/ATM co-mutation comprise a special subgroup of NSCLC patients and correlate with increasing TMB and responses to ICIs. It may have implications for potential predictive biomarker in guiding ICIs immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jian Ji Pan.
Funding
National Natural Science Foundation of China (Grant No. U1705282).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1122 - Platelets from metastatic cancer patients have increased aggregation and activation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
2671 - Luminal B breast cancer prognosis prediction by comprehensive analysis of Homeobox genes
Presenter: Ayako Nakashoji
Session: Poster Display session 3
Resources:
Abstract
2650 - Long non-coding RNA E2F4as promotes tumor progression and predicts patient prognosis in human ovarian cancer
Presenter: Sun-Ae Park
Session: Poster Display session 3
Resources:
Abstract
1462 - FGF19 promotes esophageal squamous cell carcinoma progression by inhibiting autophagy
Presenter: Lisha Ying
Session: Poster Display session 3
Resources:
Abstract
5787 - Proof of concept on the role of ex vivo lung cancer spheroids, cytokines expression and PBMCs profiling in monitoring disease history and response to treatments.
Presenter: Raimondo Di Liello
Session: Poster Display session 3
Resources:
Abstract
5253 - Circulating microRNAs related to DNA damage response as predictors of survival in metastatic non- small cell lung cancer patients treated with platinum-based chemotherapy
Presenter: Dimitris Mavroudis
Session: Poster Display session 3
Resources:
Abstract
5286 - Prognostic value of CTCs in advanced NSCLC patients treated with platinum-based chemotherapy
Presenter: Silvia Calabuig-Fariñas
Session: Poster Display session 3
Resources:
Abstract
5781 - Exosomes in NSCLC as a source of biomarkers
Presenter: Elena Duréndez
Session: Poster Display session 3
Resources:
Abstract
1447 - The role of Pim-1 in the development and progression of papillary thyroid carcinoma
Presenter: Xin Zhu
Session: Poster Display session 3
Resources:
Abstract
1323 - Development and Validation of a RNA-Seq Based Prognostic Signature in Neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster Display session 3
Resources:
Abstract