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A Comparative Analysis of Tumors and Plasma Circulating Tumor DNA in 145 Advanced Cancer Patients Annotated by 3 Core Cellular Processes

Authors
  • Larson, Kristian
  • Kannaiyan, Radhamani
  • Pandey, Ritu
  • Chen, Yuliang
  • Babiker, Hani M.
  • Mahadevan, Daruka
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Mar 16, 2020
Volume
12
Issue
3
Identifiers
DOI: 10.3390/cancers12030701
PMID: 32188081
PMCID: PMC7140098
Source
PubMed Central
Keywords
License
Green

Abstract

Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy. We collected NGS data on 145 patients who have failed standard therapy (2016 to 2018). One hundred and forty two patients had data for tissue (Caris MI/X) and plasma cell-free circulating tumor DNA (Guardant360) platforms. The mutated genes were categorized into cell fate (CF), cell survival (CS), and genome maintenance (GM). Comparative analysis was performed for concordance and discordance, unclassified mutations, trends in TP53 alterations, and PD-L1 expression. Two gene mutation maps were generated to compare each NGS platform. Mutated genes predominantly matched to CS with concordance between Guardant360 (64.4%) and Caris (51.5%). TP53 alterations comprised a significant proportion of the mutation pool in Caris and Guardant360, 14.7% and 13.1%, respectively. Twenty-six potentially actionable gene alterations were detected from matching ctDNA to Caris unclassified alterations. The CS core cellular process was the most prevalent in our study population. Clinical trials are warranted to investigate biomarkers for the three core cellular processes in advanced cancer patients to define the next best therapies.

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