Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells

Abstract

Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. Sequencing of 18 CTC samples (median: 4 CTCs/sample) from 10 HCC patients using a low-resolution whole-genome sequencing strategy (median: 0.88 million reads/sample) revealed frequent SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/ 44 (73%) CTCs from 12/16 (75%) patients with different cancer types.

Circulating tumor cells: A step toward precision medicine in hepatocellular carcinoma

“…incorporated laser microdissection technology to isolate single CTCs for profiling somatic copy number alterations (SCNAs). There was an 80% concordance of SCNA profiling between HCC CTCs and primary tumors 62 . Sun et al .…”

“…There was an 80% concordance of SCNA profiling between HCC CTCs and primary tumors. 62 Sun et al displayed that the CTCs purified by the latest NanoVelcro assay, that is, Click Chip, possessed highly concordant expression of 64 HCC tissue-derived genes from The Cancer Genome Atlas (TCGA). 14 Lee et al established a 10-gene HCC CTC Risk Score panel (DDR1, EHHADH, AR, LUM, HSD17B6, PMEPA1, TSKU, NECAB2, LAD1, and SLC27A5) quantified by the NanoString nCounter platform 65 and the risk score was significantly associated with overall survival.…”

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

“…Genetic analysis showed that CTCs derived from advanced-stage HCC tissues have HER-2 amplification and TP53 deletion. Using the Cancer Genome Atlas (TCGA)-based SCNA profiling, tumor tissue origination was confirmed for 73% of CTCs from 75% of cancer patients (71).…”

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer

“…Importantly, sequencing studies exploring the genomic landscape of CTCs (Chemi et al 2019; Gulbahce et al 2017; Magbanua et al 2018; Court et al 2020) have shown that the mutational profiles of CTCs generally reflects the overall genomic composition of matched primary and metastatic lesions. Collectively, these results suggest that CTC diversity represents the overall tumor heterogeneity probably better than single tumor tissue biopsies, and incorporating CTC genomic information is expected to increase the clinical value of liquid biopsies by providing better predictions of therapeutic sensitivity and survival outcome (Pailler et al 2019; Paoletti et al 2018).…”