Genomics Inform.  2017 Mar;15(1):48-50. 10.5808/GI.2017.15.1.48.

Circulating Tumor DNA in a Breast Cancer Patient's Plasma Represents Driver Alterations in the Tumor Tissue

• Lee J
• Cho SM
• Kim MS
• Lee SH
• Chung YJ
• Jung SH

• KMID: 2375584
• DOI: http://doi.org/10.5808/GI.2017.15.1.48

Abstract

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.

Keyword

breast neoplasms; CDK4 amplification; circulating tumor DNA; liquid biopsy; next generation sequencing; PTEN mutation

MeSH Terms

Biopsy
Breast Neoplasms*
Breast*
DNA*
Frameshift Mutation
Gene Frequency
Plasma*
Polymerase Chain Reaction
Population Characteristics
DNA