Genetic Profile and Microsatellite Instability in a Case of Secondary Esophageal Squamous Cell Carcinoma 12 Years After Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia
Genetic Profile and Microsatellite Instability in a Case of Secondary Esophageal Squamous Cell Carcinoma 12 Years After Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia
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DOI：
10.1097/mph.0000000000001355
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发表时间：
2020-05-01
影响因子：
1.2
通讯作者：
Yuza，Yuki
中科院分区：
文献类型：
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作者：
Akiyama，Masaharu;Yamaoka，Masayoshi;Yuza，Yuki
我们报告一位16岁日本男孩，因再生障碍性贫血接受异基因造血干细胞移植后12年发生食道鳞状细胞癌。在食管鳞状细胞癌中检测到高频率的微卫星不稳定性。此外，致病性变体的检测，包括TP53（c. 346C> T）和BRCA2（c. 6952C> T）和KDM6A的剪接（c. 1194+ 2T> G），表明患者中ESCC的发展是由检查点受损和DNA损伤修复以及表观遗传修饰通过慢性移植物抗宿主病和长期施用他克莫司诱导的基因突变积累而引发的。
We report on a 16-year-old Japanese boy in whom an esophageal squamous cell carcinoma (ESCC) developed 12 years after allogeneic hematopoietic stem cell transplantation was performed for aplastic anemia. A high frequency of microsatellite instability was detected in samples of ESCC. Moreover, the detection of pathogenic variants, including single nucleotide substitution of TP53 (c. 346C> T) and BRCA2 (c. 6952C> T) and splicing of KDM6A (c. 1194+ 2T> G), suggest that the development of ESCC in the patient was triggered by impairment of checkpoint and repair for DNA damage and epigenetic modification through accumulation of gene mutations induced by chronic graft-versus-host disease and prolonged administration of tacrolimus.