Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized Treatments in Multiple Cancer Types

Abstract

Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.

From validity to clinical utility: the influence of circulating tumorDNAon melanoma patient management in a real‐world setting

“…These results mirror previous findings that ctDNA was frequently undetectable in the blood of patients with cancers that originate from or metastasize to the central nervous system (Bettegowda et al ., , De Mattos‐Arruda et al ., ; Momtaz et al ., ). While efforts are underway by several groups to improve the performance characteristics of various ctDNA detection methods, there may be some patients for whom ctDNA might not be a suitable biomarker based on tumor burden, location, or biology (Aravanis et al ., ; Bettegowda et al ., , Shu et al ., ). These patients require the continued use of surveillance imaging to assess disease status.…”

Genotyping of circulating cell‐free DNA enables noninvasive tumor detection in myxoid liposarcomas

“…In contrast, detection of copy number variation in peripheral blood has a lower sensitivity (ctDNA burden >1–5%), as ctDNA is only indirectly quantified by assessing the amplified gene relative to a reference gene . Additionally, detection depends substantially on the rate of amplification, which is variable in DDLS and WDLS.…”

Genomic profiling of synchronous triple primary tumors of the lung, thyroid and kidney in a young female patient: A case report

“…Sequencing libraries were prepared using the KAPA Hyper Prep kit (KAPA Biosystems Inc., Wilmington, MA, USA) with recommended standard protocol. Hybridization capture was carried out following the methods as previously described (2). The target-enriched library was then sequenced on HiSeq4000 NGS platforms (Illumina, San Diego, CA, USA).…”

“…Detailed data analysis methods were discussed in Shu et al (2). Briefly, sequencing reads were mapped to the reference sequence hg19 (Human Genome version 19) using Burrows-Wheeler Aligner (BWA-mem, version 0.7.12) (3).…”