Abstract 1961P
Background
PTPRT (Protein Tyrosine Phosphatase Receptor Type T) is a commonly mutated gene in cancer according to TCGA. Here, we describe the prevalence of PTPRT in Chinese patients with solid tumors and its correlation with tumor mutational burden (TMB) and PD-L1 expression.
Methods
Next-generation sequencing (NGS) was performed via a 733-gene panel on FFPE tumor samples from 4360 Chinese pan-cancer patients. Single-nucleotide variants, insertions/deletions, copy number variations, gene rearrangements, tumor mutation burden (TMB) and microsatellite status were evaluated. PD-L1 expression was assessed by VENTANA SP263 assay. The MSKCC pan-cancer cohort treated with immune checkpoint inhibitors (ICIs; PMID: 30643254) was downloaded from cBioPortal.
Results
In total, 192/4360 (4.4%) patients harbored one or more PTPRT non-synonymous mutations. PTPRT mutations commonly occurred in multiple cancer types including bladder/urinary tract (16/143, 11.2%), endometrium (5/60, 8.3%), colorectum (43/584, 7.4%), esophagus (5/76, 6.6%), stomach (15/275, 5.5%), ovary (6/123, 4.9%), lung (58/1233, 4.7%), cervix (2/50, 4.0%) and head and neck (3/76, 3.9%). Among PTPRT mutations, missense was the most frequent (83.7%), followed by frameshift indel (6.1%), nonsense (6.1%), non-frameshift indel (2.0%), and splice (2.0%). Most of these data was similar to the TGCA data. However, lower frequency was found in stomach (5.5% vs 11.6%) and lung (4.7% vs 9.0%), and higher frequency was found in bladder/urinary tract (11.2% vs 4.1%) and ovary (4.9% vs 1.5%). In pan-cancer MSS patients, tumors harboring PTPRT mutations have significantly higher TMB (median 11 vs 5 muts/Mb, p<0.0001) and higher frequency of positive PD-L1 expression (p=0.0015). In MSKCC pan-cancer cohort, prolonged overall survival (HR 0.54, 95% CI 0.41 to 0.72) and higher TMB (median 22 vs 6 muts/Mb, p<0.0001) was observed in patients harboring PTPRT mutations.
Conclusions
We first described the prevalence of PTPRT mutation and its correlation with TMB and PD-L1 expression in a large Chinese solid tumor cohort. PTPRT mutation may play a role in predicting clinical benefit of ICIs therapy in pan-cancer patients. Further prospective validation is needed in the future.
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.