TP53胚系突变致横纹肌肉瘤继发急性淋巴细胞白血病1例并文献复习  

Acute lymphoblastic leukemia after rhabdomyosarcoma caused by germline TP53 mutation:a case report and literature review

作　　者：陈开澜[1] 王群[1] 陶芳 李建新[1] 李晖[1] Chen Kailan;Wang Qun;Tao Fang;Li Jianxin;Li Hui(Department of Hematology and Oncology,Wuhan Children′s Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430016,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院血液肿瘤科,武汉430016

出　　处：《中华实用儿科临床杂志》2020年第18期1425-1427,共3页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的提高对TP53胚系突变有关的遗传性肿瘤的认识。方法回顾分析2019年2月武汉儿童医院收治1例横纹肌肉瘤继发急性淋巴细胞白血病病例,对患儿临床特点及基因检测进行分析,并行相关文献复习。结果患儿在9月龄时确诊为罕见的多形性横纹肌肉瘤,行单纯手术完整切除后未行化疗及放疗,7年后继发T细胞型急性淋巴细胞白血病,经突变基因检测及亲缘验证确诊存在TP53胚系突变。予长春新碱+柔红霉素+门冬酰胺酶+地塞米松(VDLD)诱导治疗,获得完全缓解。文献复习目前TP53胚系突变共1438种,主要以错义点突变为主(707种),易出现早发肿瘤,并以女性患者多见。针对TP53基因突变通路的分子靶向治疗可发挥抗肿瘤作用。结论对于早发的遗传易感性的肿瘤需要行TP53胚系突变检测,对其家系进行系统监测,以早期干预并预防第二肿瘤发生。针对肿瘤患者的TP53胚系突变的靶向药物可减低放化疗毒性作用而获得有效的治疗。Objective To understand the hereditary cancer related to germline TP53 mutations.Methods A retrospective analysis was performed on a case of acute lymphoblastic leukemia(ALL) secondary to rhabdomyosarcoma admitted to Wuhan Children′s Hospital in February 2019.The clinical characteristics and gene detection were analyzed, and the correlative literature was studied.Results The patient was diagnosed with rarely pleomorphic rhabdomyosarcoma at the age of 9 months, and only underwent complete excision without subsequent chemotherapy and radiotherapy.Seven years later, without exposure to suspicious carcinogenic risk factors, she was suffered from secondary ALL, germline TP53 mutations were confirmed by mutation gene detection and genetic verification.She received the induction treatment with Vincristine+ Daunorubicin+ L-Asparaginase+ Dexamethasone(VDLD), and then achieved the complete remission.According to the literature review result, there were 1 438 mutations emerging in TP53 gene, which were dominant by missense point mutations (707 kinds). These mutations could result in early-onset tumors that commonly arose in female patients.Molecular targeted therapy through TP53 gene mutation pathway could resist tumors.Conclusions Germline TP53 mutation screening should be recommended for the early-onset tumor with genetic predisposition, and systematical monitoring of the family is also suggested, so as to early intervene and prevent the occurrence of the second tumor.The targeted drugs for germline TP53 mutations can reduce the toxicity of radiotherapy and chemotherapy and achieve high treatment effects.

关 键 词：TP53基因 胚系突变 继发肿瘤 Li-Fraumeni综合征 

分 类 号：R733.71[医药卫生—肿瘤] R738.7[医药卫生—临床医学]