Lab Med Qual Assur.  2021 Mar;43(1):25-30. 10.15263/jlmqa.2021.43.1.25.

Frequency of Benign Variants Associated with Hematologic Malignancy in the Catalogue of Somatic Mutations in Cancer

• Park KJ
• Park JH

• KMID: 2514598
• DOI: http://doi.org/10.15263/jlmqa.2021.43.1.25

Abstract

Background
The presence of benign variants in mutation databases is a well-documented pitfall when interpreting clinical variants associated with hematologic malignancy. The aim of this study was to investigate the frequency of benign or likely benign (B/LB) variants associated with hematologic malignancy in the Catalogue of Somatic Mutations in Cancer (COSMIC), which is one of the most commonly used databases for cancer.
Methods
A total of 12,149,816 coding variants were downloaded from COSMIC (release ver. 91, April 2020), and 123,211 variants in 99 genes associated with hematologic malignancy were analyzed. The genes were selected according to the criteria recommended by the World Health Organization and National Comprehensive Cancer Network guidelines. The variant classification was performed based on standardized interpretation guidelines.
Results
The frequency of B/LB variants was 3.2% (3,890/123,211) of the COSMIC variants. In addition, 44.9% (1,748/3,890) of B/LB variants were observed in at least two cancer samples. In terms of drug response and cancer susceptibility, 2.9% (112/3,890) of the B/LB variants were clinically significant.
Conclusions
This study revealed that a significant number of B/LB variants were registered in COSMIC. This study highlights the importance of the reinterpretation of cancer variants reported from mutation databases and could be a good starting point for an in-depth review of somatic mutations essential for precision oncology.

Keyword

Catalogue of Somatic Mutations in Cancer; Database; Mutation