Novel Genetic Biomarkers of Chemotherapeutic Response in Canine Lymphoma and Improved Predictive Power With Integration of Machine Learning

October 17, 2024

Presentation Detail

PresenterSushmita Sen, Senior Research Associate, ImpriMed, Inc.

Research Abstract

Introduction
Predicting treatment outcomes and prognosis remains a significant challenge in canine lymphoma. Recent studies suggest mutations in key oncogenic, tumor suppressor, and pharmacogenomic genes can impact the course of lymphoproliferative disease. Our current study aims to identify mutations in the genomic landscape that correlate with immunophenotype-specific outcomes for multi- or single-agent regimens.

Methods
We performed PARR, flow cytometry, and paired tumor-normal targeted NGS sequencing on 238 canines selected from our biobank of >6,000 samples. The targets were 308 known or suspected cancer-related genes. The sequencing results included somatic and germline variants and longitudinal data evaluated for differences in covariate-related survival based on mutational features.

Results
We have identified putative biomarkers that correlate with clinical outcomes in specific lymphoma immunophenotypes. In B-cell, we identified four mutated genes associated with a clinical response for CHOP/L-CHOP or Tanovea-based regimens (p<0.05). In T-cell, we identified four mutated genes related to clinical response for CHOP/L-CHOP or lomustine-based regimens (p<0.05). Adding to our previous findings for mutated “Predictor of Slow Relapse-1” (PSR-1), for naïve B-cell lymphoma we found an extended progression-free survival (p=0.026), longer overall survival (p=0.042), and a trend towards a longer duration of response (p=0.052).

Conclusion
We have previously presented our personalized prediction platform converging molecular features, live-cell drug sensitivity, and AI to support treatment decisions. In this new study, we introduce promising gene targets that can serve as subtype- or treatment-specific biomarkers. These results demonstrate how comprehensive genomic profiling, as a precision medicine tool, could improve the management of canine lymphoma.

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