PTPRT mutation

The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations.

In summary, our findings reveal the mechanism of how PTPRT-deficient tumors become sensitive to anti-PD-1 therapy and highlight the biological function of PTPRT in innate immunity. Considering the prevalence of PTPRT mutations and negative expression, this study has great value for patient stratification and clinical decision-making.

Our findings uncovered the essential roles of PTPRT in the regulation of proliferation, migration, and invasion of LUAD, and highlighted the clinical significance of PTPRT downregulation in lung cancer.

The antibody-drug conjugate ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. A molecular response was observed in 48% (14/29) of all evaluated pts and 47% (8/17) of pts with CRC; median change from baseline tumor size was -22.5% and -20.3%, respectively. Table: 163P Pts with molecular response and correlation between baseline biomarker status and radiographic response Conclusions ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including in pts with high TMB and KRAS mutations.

Combining clinical features with genetic analysis, we found that patients carrying both DNA POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate. Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.

Based on the risk score of the model, patients in the low-risk group showed a better mOS than those in the high-risk group (mOS: 2.75 vs 1.08 years, HR = 0.567, 95%CI: 0.492-0.654; P < 0.001). PTPRD/PTPRT mutations may be a potential biomarker for predicting ICI treatment responsiveness in multiple cancer types.

A combined analysis using a dataset from the genomics evidence neoplasia information exchange (GENIE) and cBioPortal revealed that PTPRT mutation is associated with poor prognosis in pan-cancer and non-small-cell lung cancer. The mutations of PTPRT or "gene modules" containing PTPRT are significantly enriched in patients with metastatic cancer in multiple cancers, suggesting that the PTPRT mutations serve as potential biomarkers of cancer metastasis.

Our investigation indicates that PTPRT mutations may be considered as a potential indicator for assessing ICI efficacy in melanoma and NSCLC, even across multiple cancers. Further prospective validation cohorts are warranted.

Next generation sequencing showed that TERT mutations commonly co-existed with other driver genes. Our finding expands the mutant spectrum of TERT gene and adds new understanding of the phenotype.

This work suggested that PTPRD/PTPRT mutation might be a potential positive predictor for ICBs in NSCLC. These results need to be further confirmed in future.