Fang Hua, Yue Hu, Guang-Cui He, Si-Han Lai, Ying He, Shan Zhang, Yan Deng, Ying Han, Xiao-Dong Liu, Kun Yang, Hui-Xiu Zhong, Jian Xiao, Zhong-Zheng Zheng, Hai Yi
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Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free.</p><p><strong>Conclusion: </strong>This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2377860"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.\",\"authors\":\"Fang Hua, Yue Hu, Guang-Cui He, Si-Han Lai, Ying He, Shan Zhang, Yan Deng, Ying Han, Xiao-Dong Liu, Kun Yang, Hui-Xiu Zhong, Jian Xiao, Zhong-Zheng Zheng, Hai Yi\",\"doi\":\"10.1080/16078454.2024.2377860\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Backgroud: </strong>Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. 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引用次数: 0
摘要
背景介绍Li-Fraumeni综合征是一种遗传性肿瘤综合征,其特点是发生恶性肿瘤,尤其是急性淋巴细胞白血病(ALL)的风险较高,可由杂合种系突变引起。TP53基因种系突变被认为是急性白血病发生和诊断的潜在危险因素和重要预后参数,但很少发生在成人中,其在急性白血病中的具体致病意义尚不清楚:我们描述了一例被诊断为 ALL 的 45 岁女性病例。全外显子组测序方法从她的骨髓样本中发现了一个可能具有致病意义的TP53种系突变,即位于第8外显子上的c.848G>A(p.Arg283His)杂合错义突变,并在她的头发、口腔粘膜和指甲样本中得到了进一步验证。家族血统筛查显示,患者的父亲和非捐献者的儿子存在相同的 TP53 基因变异,而捐献者则没有。数字聚合酶链式反应(Digital PCR)观察到,移植后该点突变频率下降,但在维持治疗期间,当患者无白血病时,该点突变频率仍然很低:结论:这例疑似李-弗劳米尼综合征病例报告中可能存在致病性杂合子 TP53 变异,从而扩大了癌症基因谱。对她的家庭成员进行基因突变筛查,有助于确定最佳亲属捐赠者,并通过监测造血干细胞移植后最小残留病的TP53种系突变,避免不必要的治疗。其在血液恶性肿瘤发展中的潜在作用和临床致病影响还需要进一步探究。
Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.
Backgroud: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear.
Case presentation: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free.
Conclusion: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.
期刊介绍:
Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.