Secondary Germline CDKN2A Mutation Identified using Liquid Biopsy in a Patient with Esophageal Cancer

Abstract

Liquid biopsy is a non-invasive method for tumor genotyping through detecting the circulating tumor DNA (ctDNA). Here, we describe the case of an esophageal squamous cell cancer patient in which a germline CDKN2A mutation was identified incidentally through liquid biopsy. The preoperative sample analysis revealed a total of five alterations in CDKN2A, TP53, FAT1, and KMT2C genes using next-generation sequencing data. The CDKN2A p.R87W was confirmed as a germline mutation, which is likely a pathogenic variant revealed through peripheral leukocyte DNA analysis. The patient underwent esophagectomy and sequential adjuvant chemoradiation therapy. After the surgery, the variant allele frequencies of somatic variants tended to decrease throughout the treatment. In addition to the detection of somatic variants, ctDNA testing can also provide information on the germline cancer susceptibility variants.