Letter to the Editor
Ann Lab Med 2022; 42(3): 380-383
Published online May 1, 2022 https://doi.org/10.3343/alm.2022.42.3.380
Copyright © Korean Society for Laboratory Medicine.
RNA Sequencing Provides Evidence for Pathogenicity of a Novel CHEK2 Splice Variant (C.1009-7T>G)
Departments of 1Laboratory Medicine and 2Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to: Woochang Lee, M.D.
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel.: +82-2-3010-4506, Fax: +82-2-478-0884
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.
Prostate cancer is common worldwide and is the fourth most common cancer in Korean men . Although the exact cause of prostate cancer is unknown, its incidence is higher among certain ethnicities, in the elderly, and in individuals with a family history . Inherited variants in several DNA repair genes, including
In 2021, a 70-year-old man undergoing chemotherapy for metastatic prostate cancer without a known family history showed a continuous increase in prostate-specific antigen (PSA). After obtaining informed consent, NGS was performed for 171 hereditary tumor-related genes for further evaluation and management at Asan Medical Center, Seoul, Korea. Genetic testing was performed as a clinical laboratory test and not with a research objective; approval from the Institutional Review Board was exempted. Genomic DNA was extracted from peripheral blood leukocytes using a customized target enrichment kit (Dxome, Seongnam, Korea), and NGS was conducted on a MiSeqDx instrument (Illumina, San Diego, CA, USA) using a MiSeqDx V2 sequencing kit (Illumina).
The mean coverage depth was 554.2×. Except for one intronic variant in
Figure 1. Next-generation sequencing revealed a variant of
CHEK2, involving a substitution of thymine (T) for guanine (G) at the intron located –7 from the acceptor site (c.1009T>G).
Given the implication of
Figure 2. RNA sequencing revealed exon 10 skipping. This variant is represented as NM_007194.4(
As clinical sequencing is mostly performed at the DNA level, disease-causing splicing variants may be underestimated . The presence of numerous VUS compromises a precise assessment of the risk associated with particular tumor types . RNA sequencing was performed to find evidence of PS3 in a suspected splice variant, which confirmed an in-frame deletion caused by exon 10 skipping. The VUS was reclassified as PM1 and PM4, rather than PS3. RNA sequencing should be more actively considered to provide additional evidence for the determination of pathogenicity categories other than PS3.
Na R wrote the manuscript. Lee J managed the patient and provided the clinical information. Hong J, Gu H, Lee W, and Min W contributed to the interpretation of the results, and the writing and revision of the manuscript.
CONFLICTS OF INTEREST
No potential conflicts of interest relevant to this paper are reported.
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