식도암 환자에서 액체생검을 통해 확인된 이차 생식세포 CDKN2A 돌연변이: 증례보고
Secondary Germline CDKN2A Mutation Identified using Liquid Biopsy in a Patient with Esophageal Cancer
연세대학교 의과대학 진단검사의학교실1, 흉부외과학교실2
Departments of Laboratory Medicine1 and Thoracic and Cardiovascular Surgery2, Yonsei University College of Medicine, Seoul, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2022; 12(1): 63-67
Published January 1, 2022
Copyright © The Korean Society for Laboratory Medicine.
Non-invasive tumor genotyping using circulating tumor DNA (ctDNA), or liquid biopsy, has been used increasingly in the clinical oncology field for cancer diagnosis, monitoring, and assessing the eligibility of the targeted therapy. Since a large part of the cell-free DNA (cfDNA) in plasma originates from the non-tumor cells, such as leukocytes, next-generation sequencing (NGS) using cfDNA for somatic variants of a solid tumor can help identify the germline variants at approximately 50% (heterozygous) or 100% (homozygous) variant allele frequency (VAF). Therefore, using liquid biopsy, the germline heterozygous pathogenic variants of cancer susceptibility genes can be identified incidentally with about 50% VAF, whereas somatic variants typically exhibit lower VAFs [1-4].
The cyclin-dependent kinase inhibitor 2A (
Here, we describe the case of a patient with esophageal squamous cell cancer in which a germline
A 60-year-old male patient was diagnosed with upper esophageal squamous cell carcinoma through endoscopic biopsy after visiting an outside hospital with a one-month history of dyspepsia and nausea. The patient had a medical history of premature atrial contraction and smoking history of 10 pack-years. He also had a family history of maternal breast cancer and biliary cancer. The clinical stage based on the preoperative imaging analysis was confirmed as cT3N2. With the patient’s consent, he was enrolled in an observational study to predict the postoperative recurrence of eso-phageal cancer using liquid biopsy.
The preoperative blood collection followed by NGS analysis targeting 27 genes associated with esophageal cancer, including
Figure 1. Changes in the variant allele frequencies of somatic variants throughout the treatment. The somatic variants identified at the initial liquid biopsy exhibited a decreasing tendency throughout the treatment. The somatic variants were classified based on the 2017 Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists guidelines . The variant allele frequency (VAF, %) was calculated as (read depth count of identified variant/total read depth count at the position)×100.
Abbreviations: T, Tier; VAF, variant allele frequency; XP, cisplatin and capecitabine chemotherapy.
The patient underwent esophagectomy and total mediastinal lymph node dissection, while cervical esophagogastrostomy and pathologic reports revealed that he was at the final stage of upper esophageal cancer, poorly differentiated pT3N3, based on the 8th edition of the AJCC TNM cancer staging system . The patient received sequential adjuvant chemoradiation therapy with cisplatin and capecitabine (XP). During nine months of follow-up, he exhibited no clinical or radiological signs of tumor recurrence or metastasis. Serial liquid biopsies were performed at 25, 105, and 180 days after surgery. A germline
The NCCN guideline for genetic testing recommends pancreatic cancer screening for individuals with a known pathogenic/likely pathogenic variant of
There have been several reports on the identification of secondary germline mutations in cancer predisposition genes through ctDNA testing [1, 2, 4, 23]. Slavin et al.  recently reported an extensive data set on secondary germline cancer predisposition mutations in cancer patients who underwent commercial cfDNA testing. As a result, the germline hereditary cancer mutations were observed in 11 genes in 1.4% of patients. In the study, 10
The other somatic variants in
The limitation of our report is that we could not perform genetic testing in affected family members to confirm the causal role of the
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