Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies. Mol Cancer Ther 2019 May;18(5):1001-1011
Date
03/31/2019Pubmed ID
30926636DOI
10.1158/1535-7163.MCT-17-1038Scopus ID
2-s2.0-85065511969 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
Clinical-grade next-generation sequencing (NGS) of tissue- and blood-derived circulating tumor DNA (ctDNA) allows assessment of multiple genomic alterations in patients with cancer. We analyzed ctDNA (54-70 genes) in 62 patients with advanced breast cancer (median = five prior therapies); 38 also had tissue NGS (236-315 genes). Overall, 42 of 62 patients (68%) had detectable (characterized) ctDNA alterations (variants of unknown significance excluded), and 37 of 38 (97%) had tissue alterations. The median (range) number of characterized alterations in ctDNA was 1 (0-7), and in tissue, 4 (0-17). The most common alterations in ctDNA were in TP53 (37% of patients) and PIK3CA (23%), and for tissue, TP53 (37%) and PIK3CA (24%); EGFR amplification was seen in ctDNA (11%), but not in tissue. Concordance between ctDNA and tissue appeared higher if <6 months separated the sample acquisition, although small sample size precluded statistical validation. Overall, 32 of 67 tissue alterations (48%) were also detected in ctDNA; 35 of 72 ctDNA alterations (48%) were also in tissue. Excluding estrogen receptor and ERBB2, 41 of 62 patients (66%) had potentially actionable alterations in ctDNA, and 36 of 38 (95%), in tissue (with potential actionability based on either preclinical or clinical evidence). If ≥1 genomic alteration had ctDNA ≥5%, survival was shorter than if ctDNA was <5% (median, 6.7 vs. 17.9 months; P = 0.01). In conclusion, tissue and ctDNA NGS reveal potentially actionable alterations in most patients. The genomic results of ctDNA and tissue NGS overlap, but there are differences, perhaps reflecting temporal spacing and tumor heterogeneity. ctDNA quantification also provides prognostic information.
Author List
Shatsky R, Parker BA, Bui NQ, Helsten T, Schwab RB, Boles SG, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorBreast Neoplasms
Cell Line, Tumor
Circulating Tumor DNA
Female
Genome, Human
Genomics
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation