Genome-wide Profiling of Circulating Tumor DNA Depicts Landscape of Copy Number Alterations in Pancreatic Cancer with Liver Metastasis

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2020 Jun 28

PMID 32593194

Citations 11

Authors

Tao Wei

Jian Zhang

Jin Li

Qi Chen

Xiao Zhi

Wei Tao

Jingjiao Ma

JiaQi Yang

Yu Lou

Tao Ma

Xiang Li

Qi Zhang

Wei Chen

Risheng Que

Shunliang Gao

Xueli Bai

Tingbo Liang

Affiliations

Soon will be listed here.

Abstract

Cell-free DNA (cfDNA) offers an alternative to tissue biopsies for genomic profiling in tumors. Here, we sought to evaluate copy number alterations in PDAC through whole-genome sequencing (WGS) of cfDNA and determine their clinical significance. Using shallow WGS across 90 plasma samples from 70 pancreatic cancer patients, we detected somatic copy number alterations (CNAs) in 34 subjects (48.6%). Additionally, a higher tumor fraction (TFx) was associated with increased carbohydrate antigen 19-9 (CA19-9), metastasis, and a worse prognosis. Serial cfDNA analysis suggested that CNAs were highly concordant even for progressive disease after chemotherapy. TFx dynamics were largely in line with changed CA19-9 levels and tumor burden following chemotherapy. Notably, patients with more abundant, baseline CNAs exhibited a better response to chemotherapy. In conclusion, shallow WGS for cfDNA enables a high-throughput characterization of CNAs and an estimation of tumor burden in metastatic pancreatic cancer. These findings reinforce our understanding of the genomic evolution of metastatic PDAC and might have clinical relevance for guiding treatment.

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