Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Cancer Genet. 2022 Apr;262-263:95-101. doi: 10.1016/j.cancergen.2022.02.002. Epub 2022 Feb 11.
Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary cancer syndrome characterized by hundreds to thousands of colorectal adenomatous polyps. Without treatment, progression to colorectal cancer is inevitable. Most pathogenic mutations in the APC gene were nonsense or frameshift mutations; however, some previous studies reported large deletions or duplications.
We reviewed the results of APC gene analyses from January 2010 to December 2020. We analyzed the entire coding sequence of the APC gene by Sanger sequencing to detect genetic abnormalities. Moreover, multiplex ligation-dependent probe amplification (MLPA) testing was performed starting in September 2017, and a multigene panel study that includes the APC gene was begun in July 2019.
In the 266 collected cases, pathogenic variants/likely pathogenic variants (PV/LPVs) in the APC gene were detected in 73 patients, and variants of uncertain significance were found in 13 patients. Among those variants, 14 variants were novel. We performed MLPA for 29 patients, and 7 of them (24.1%) were positive for a large duplication/deletion. Among the 73 cases in the multigene panel study, 17 cases (23.3%) of APC gene variation were detected.
We retrospectively analyzed the APC gene in Korean patients suspected to have FAP. Variants truncated by nonsense and frame shift mutations were common PV/LPVs. However, the detection rate in the MLPA study was higher than in previous studies of Caucasian populations. We suggest that MLPA should be performed for patients likely to have FAP but in whom no variant is detected by sequencing methods.
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传的癌症综合征，其特征是大肠中有数百到数千个腺瘤性息肉。如果不治疗，发展为结直肠癌是不可避免的。APC 基因中的大多数致病突变是无义或移码突变；然而，一些先前的研究报告了大片段缺失或重复。
我们回顾了 2010 年 1 月至 2020 年 12 月期间 APC 基因分析的结果。我们通过 Sanger 测序分析 APC 基因的整个编码序列，以检测遗传异常。此外，自 2017 年 9 月开始进行多重连接依赖性探针扩增（MLPA）检测，自 2019 年 7 月开始进行包括 APC 基因在内的多基因panel 研究。
在 266 例送检病例中，在 73 例患者中检测到 APC 基因的致病性变异/可能致病性变异（PV/LPVs），在 13 例患者中发现了意义不明的变异。在这些变异中，有 14 种是新的。我们对 29 例患者进行了 MLPA，其中 7 例（24.1%）存在大片段重复/缺失。在多基因panel 研究的 73 例中，检测到 17 例（23.3%）APC 基因变异。
我们回顾性分析了疑似 FAP 的韩国患者的 APC 基因。无义突变和移码突变截断的变异是常见的 PV/LPVs。然而，MLPA 研究的检出率高于以前的白人人群研究。我们建议对通过测序方法未检出变异的疑似 FAP 患者进行 MLPA 检测。
