Abstract

Abstract Accurately diagnosing the tumor histological subtype is crucial for clinical care. Changes in subtype can emerge during treatment resistance. However, obtaining a biopsy to determine the tumor histology presents challenges for patients with advanced cancers. Circulating tumor DNA (ctDNA) is a non-invasive 'liquid biopsy' solution that overcomes this limitation of tissue accessibility. Current ctDNA approaches primarily focuses on detecting genetic mutations, but these alterations alone may not fully delineate tumor histological subtypes or explain treatment resistance. Recent advancements highlight the value of epigenetic information obtained from profiling nucleosome positioning and accessibility in ctDNA. I will discuss how we applied these concepts to develop computational methods for predicting transcriptional activity and classifying tumor subtypes and phenotypes in breast, prostate, and lung cancers. These tools have applications in monitoring treatment-induced phenotype changes and expand on the utility of ctDNA for precision oncology. Citation Format: Gavin Ha. Methods for tumor subtype classification using cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA026.

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