title: Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA.
abstract: Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9-93.9%. However, the concordance rate decreased to 11.8-17.1% when considering only genes with reported genomic alterations in either assay. Over 50% of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1% and 94.8%, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Young Kwang
authors: YK
authors: Chae
authors: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Andrew A
authors: AA
authors: Davis
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Benedito A
authors: BA
authors: Carneiro
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Sunandana
authors: S
authors: Chandra
authors: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Nisha
authors: N
authors: Mohindra
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Aparna
authors: A
authors: Kalyan
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Jason
authors: J
authors: Kaplan
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Maria
authors: M
authors: Matsangou
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Sachin
authors: S
authors: Pai
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Ricardo
authors: R
authors: Costa
authors: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Borko
authors: B
authors: Jovanovic
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Massimo
authors: M
authors: Cristofanilli
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
authors: Leonidas C
authors: LC
authors: Platanias
authors: Developmental Therapeutics Program of Division of Hematology Oncology, Northwestern University, Chicago, IL, USA.|Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: Francis J
authors: FJ
authors: Giles
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D001706:Biopsy; D000073888:Cell-Free Nucleic Acids / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D057089:Pathology, Molecular; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C000614131:CDKN2A protein, human; D000073888:Cell-Free Nucleic Acids; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C117307:KRAS protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: cell-free DNA; genomic alterations; lung cancer; metastatic disease; next-generation sequencing