ArticleGenome medicine2021
Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 57 citations in OpenAlex.
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- Neoadjuvant Nivolumab with or without Ipilimumab for Cisplatin-Ineligible Patients with Muscle-Invasive Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma.Journal for immunotherapy of cancer · 2025Trial
- A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP).British journal of cancer · 2026Article
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Generalizable cancer detection from ultra-low-pass WGS via deep contextual modeling of cfDNA sequences.Molecular biomedicine · 2026Article
- Liquid biopsy in Oncology: Results of a Delphi consensus study endorsed by the AIOM-SIAPEC/IAP-SIBioC-SIF Italian scientific societies.The journal of liquid biopsy · 2026Article
- A computational framework for sensitive tumor detection and accurate subtyping using shallow cell-free DNA methylome sequencing.Genome medicine · 2026Article
- Nanotechnology-Assisted Molecular Profiling: Emerging Advances in Circulating Tumor DNA Detection.International journal of nanomedicine · 2026Review
- Genomic landscape of hormone therapy-resistant HR-positive, HER2-negative breast cancer.Breast cancer research and treatment · 2025Article
- Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling.The journal of liquid biopsy · 2025Article
- Baseline levels and dynamic changes of cfDNA, tumor fraction and mutations to anticipate the clinical course of small cell lung cancer (SCLC) patients treated with first-line atezolizumab and chemotherapy: an hypothesis generating study (CATS/ML43257).Journal of experimental & clinical cancer research : CR · 2025Article
- Circulating Tumor DNA and Response to Cisplatin-based Chemotherapy in Patients with Metastatic Urothelial Carcinoma Enrolled in CALGB 90601 (Alliance).European urology open science · 2025Article
- Cell-Free DNA: Features and Attributes Shaping the Next Frontier in Liquid Biopsy.Molecular diagnosis & therapy · 2025Review
- A perspective review on the systematic implementation of ctDNA in phase I clinical trial drug development.Journal of experimental & clinical cancer research : CR · 2025Review
- Can a Liquid Biopsy Detect Circulating Tumor DNA With Low-passage Whole-genome Sequencing in Patients With a Sarcoma? A Pilot Evaluation.Clinical orthopaedics and related research · 2025Article
- Article
- Liquid biopsy in cancer diagnosis and prognosis: a paradigm shift in precision oncology.Frontiers in molecular biosciences · 2025Review
- Binary classification of copy number alteration profiles in liquid biopsy with potential clinical impact in advanced NSCLC.Scientific reports · 2024Article
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Authors and funding
37 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the fraction of circulating DNA in plasma that is tumor-derived (i.e., cfDNA tumor fraction). We hypothesized that cfDNA tumor fraction could inform the interpretation of negative cfDNA results and guide the choice of subsequent assays of greater genomic breadth or depth.
methodsPlasma samples collected from 118 metastatic cancer patients were analyzed with cf-IMPACT, a modified version of the FDA-authorized MSK-IMPACT tumor test that can detect genomic alterations in 410 cancer-associated genes. Shallow whole genome sequencing (sWGS) was also performed in the same samples to estimate cfDNA tumor fraction based on genome-wide copy number alterations using z-score statistics. Plasma samples with no somatic alterations detected by cf-IMPACT were triaged based on sWGS-estimated tumor fraction for analysis with either a less comprehensive but more sensitive assay (MSK-ACCESS) or broader whole exome sequencing (WES).
resultscfDNA profiling using cf-IMPACT identified somatic mutations in 55/76 (72%) patients for whom MSK-IMPACT tumor profiling data were available. A significantly higher concordance of mutational profiles and tumor mutational burden (TMB) was observed between plasma and tumor profiling for plasma samples with a high tumor fraction (z-score≥5). In the 42 patients from whom tumor data was not available, cf-IMPACT identified mutations in 16/42 (38%). In total, cf-IMPACT analysis of plasma revealed mutations in 71/118 (60%) patients, with clinically actionable alterations identified in 30 (25%), including therapeutic targets of FDA-approved drugs. Of the 47 samples without alterations detected and low tumor fraction (z-score<5), 29 had sufficient material to be re-analyzed using a less comprehensive but more sensitive assay, MSK-ACCESS, which revealed somatic mutations in 14/29 (48%). Conversely, 5 patients without alterations detected by cf-IMPACT and with high tumor fraction (z-score≥5) were analyzed by WES, which identified mutational signatures and alterations in potential oncogenic drivers not covered by the cf-IMPACT panel. Overall, we identified mutations in 90/118 (76%) patients in the entire cohort using the three complementary plasma profiling approaches.
conclusionscfDNA tumor fraction can inform the interpretation of negative cfDNA results and guide the selection of subsequent sequencing platforms that are most likely to identify clinically-relevant genomic alterations.
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