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: Young Kwang Chae, Andrew A Davis, Benedito A Carneiro, Sunandana Chandra, Nisha Mohindra, Aparna Kalyan, Jason Kaplan, Maria Matsangou, Sachin Pai, Ricardo Costa, Borko Jovanovic, Massimo Cristofanilli, Leonidas C Platanias, Francis J Giles
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 40 Pg. 65364-65373 (Oct 04 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27588476 (Publication Type: Comparative Study, Journal Article)

Chemical References

• APC protein, human
• Adenomatous Polyposis Coli Protein
• CDKN2A protein, human
• Cell-Free Nucleic Acids
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18
• KRAS protein, human
• Tumor Suppressor Protein p53
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma (diagnosis, genetics)
• Adenomatous Polyposis Coli Protein (genetics)
• Biopsy
• Cell-Free Nucleic Acids (analysis)
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18 (genetics)
• ErbB Receptors (genetics)
• Female
• Genome
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Lung Neoplasms (diagnosis, genetics)
• Male
• Mutation (genetics)
• Pathology, Molecular
• Proto-Oncogene Proteins p21(ras) (genetics)
• Reproducibility of Results
• Sensitivity and Specificity
• Tumor Suppressor Protein p53 (genetics)