Abstract 894P
Background
ARID1A, a gene that encodes a subunit of the BAF (SWI/SNF) chromatin remodeling complex. Previous research on the ARID1A gene revealed that ARID1A deficiency was associated with a higher tumor mutation burden (TMB) level and mismatch repair (MMR) in cancer, which might cooperate with immune checkpoint blockade therapy. However, the features of ARID1A, its correlation with immunogenic marker, and the predictive value of immunotherapy for head and neck cancer remain unknown.
Methods
An independent group (the MSKCC study cohort) of next-generation sequencing (NGS) data from 129 patients with head and neck cancer, was used to analyze the prognostic effect of ARID1A on immunotherapy. Tumor tissue samples from Chinese head and neck cancer patients were analyzed using NGS (panel on 381/733-gene). TMB was defined as the total number of somatic non-synonymous mutations in the coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (Dako 22C3).
Results
In the MSKCC cohort, there were 10 (7.6%) patients who harbored ARID1A mutation. ARID 1Amutation (ARID1Amut) (median, 8.85 Muts/Mb) was associated with higher TMB (P =0.046) than PALB wild-type (ARID1A wt) (median, 5.58 Muts/Mb). In terms of prognostic effect, there was a significant difference in the overall survival (OS) (HR = 0.12, P=0.012) between ARID1A mut (median, 15.5 months) and ARID1A wt (median, 7 months). In Chinese patients, the genetic mutation of 366 head and neck cancer patients were analyzed using NGS, of which 25 (6.8%) harbored ARID1A mut. In head and neck cancer patients with ARID1A mut, the most frequently mutated genes were TP53 (72%), followed by CYP2C19 (48%), DPYD (48%), ATM (36%), and KMT2C (36%). ARID1A mut (median, 6.45 Muts/Mb) was associated with higher TMB (P =0.002) than ARID1A wt (median, 5.14 Muts/Mb), which was a significant difference. There was also a significant difference in microsatellite instability (MSI) between ARID1A mut and ARID1A wt (P＜0.001). However, there was no difference in PD-L1 expression between ARID1A mut and ARID1A wt (P =0.71).
Conclusions
The results show that the ARID1A gene has a high correlation with TMB and microsatellite instability (MSI) in head and neck cancer, and maybe a potential biomarker for immune checkpoint therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.