Tracking plasma DNA mutation dynamics in estrogen receptor positive metastatic breast cancer with dPCR-SEQ. (December 2018)

• Record Type: Journal Article
• Authors: Kumar, Sunil; Lindsay, Daniel; Chen, Q.; Garrett, Amy; Tan, Xianming; Anders, Carey; Carey, Lisa; Gupta, Gaorav
• Is Part Of: NPJ breast cancer. Volume 4(2018)
• Page Start: 1
• Page End: 5
• Publication Date: 2018-12
• Subjects: Breast -- Cancer -- Periodicals; Breast -- Cancer -- Research -- Periodicals; Breast -- Cancer -- Treatment -- Periodicals; Breast Neoplasms; Breast -- Cancer; Breast -- Cancer -- Research; Breast -- Cancer -- Treatment; Periodicals; Periodicals; 616.9944905
• DOI: 10.1038/s41523-018-0093-3
• Languages: English
• ISSNs: 2374-4677

Abstract

Abstract Serial monitoring of plasma DNA mutations in estrogen receptor positive metastatic breast cancer (ER + MBC) holds promise as an early predictor of therapeutic response. Here, we developed dPCR-SEQ, a customized assay that utilizes digital PCR-based target enrichment followed by next-generation sequencing to analyze plasma DNA mutations inESR1, PIK3CA, andTP53 . We validated dPCR-SEQ in a prospective cohort of 58 patients with ER + MBC and demonstrate excellent concordance with hotspotESR1 mutation abundance measured by conventional digital PCR. The dPCR-SEQ assay revealedESR1, PIK3CA, andTP53 plasma ctDNA mutations in 55%, 32%, and 32% of the study patients, respectively. We also observed dynamic changes inESR1, PIK3CA, andTP53 ctDNA mutant allele fraction (MAF) that were frequently discordant between the different genes. Thus, monitoring plasma DNA mutation dynamics using a dPCR-SEQ assay is feasible, accurate, and may be investigated as a biomarker of therapeutic response in ER + MBC. Genomic testing: Blood test reveals mutation dynamics in three cancer-related genes A new blood test that detects mutations in three cancer-related genes could help guide clinical decision-making for women with aggressive breast tumors. Gaorav Gupta and coworkers from the University of North Carolina at Chapel Hill, USA, developed a droplet-based microfluidic technology that replicates target genomic fragments and then sequences the DNA to quantify the fraction of gene variants that are mutated in the blood sample. The researchers designed the method to look at three genes often mutated in metastatic cases of estrogen receptor–positive breast cancer. They validated the technique using blood samples from 58 patients. In a subset of these cases, they showed that the assay, known as dPCR-SEQ, picked up changes in mutation frequency over time. These mutation dynamics could likely serve as a biomarker of therapeutic response, although clinical validation is needed.