English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

PURPOSE   Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, with more than 40% of patients initially diagnosed with multinodular HCCs. Although circulating cell-free DNA (cfDNA) has been shown to effectively detect somatic mutations, little is known about its utility to capture intratumor heterogeneity in patients with multinodular HCC undergoing systemic treatment.MATERIALS AND METHODS   Tumor biopsies and plasma were synchronously collected from seven prospectively recruited patients with HCC before and during systemic therapy. Plasma-derived cfDNA and matched germline were subjected to high-depth targeted sequencing with molecular barcoding. The mutational profile of the cfDNA was compared with whole-exome sequencing from matched tumor biopsies.RESULTS   Genomic data revealed that out of the seven patients, five were considered intrahepatic metastasis and two multicentric HCCs. cfDNA captured the majority of mutations in the tumors and detected significantly more mutations than tumor biopsies. Driver mutations such as CTNNB1 S33C, NRAS Q61R, ARID1A R727fs, and NF1 E2368fs as well as standard-of-care biomarkers of response to targeted therapy were detected only in cfDNA. In the two patients with multicentric HCC, cfDNA detected mutations derived from the genetically independent and spatially distinct nodules. Moreover, cfDNA was not only able to capture clonal mutations but also the subclonal mutations detected in only one of the multiple biopsied nodules. Furthermore, serial cfDNA detected variants of tumor origin emerging during treatment.CONCLUSION   This study revealed that the genetic analysis of cfDNA captures the intratumor heterogeneity in multinodular HCC highlighting the potential for cfDNA as a sensitive and noninvasive tool for precision medicine.

Circulating Cell-Free DNA Captures the Intratumor Heterogeneity in Multinodular Hepatocellular Carcinoma