伴DNA修复相关基因胚系突变的遗传易感性小儿白血病5例临床分析  

Clinical analysis of five leukemia children with hereditary predisposition to cancers due to germline mutations associated with DNA repair

作　　者：李娟娟[1] 岳梅[1] 钟笛箫[1] 李君惠[1] 张蕾[1] 胡涛[1] 张朝霞[1] 冯顺乔[1] 唐瑞红 胡梦泽[1] 崔小岱[2] 刘嵘[1] LI Juanjuan;YUE Mei;ZHONG Dixiao;LI Junhui;ZHANG Lei;HU Tao;ZHANG Zhaoxia;FENG Shunqiao;TANG Ruihong;HU Mengze;CUI Xiaodai;LIU Rong(Department of Hematology, Affiliated Children′s Hospital of Capital Institute of Pediatrics, Beijing 100020, China;Experiment Center,Capital Institute of Pediatrics, Beijing 100020, China)

机构地区：[1]首都儿科研究所附属儿童医院血液科,北京100020 [2]首都儿科研究所实验中心,北京100020

出　　处：《中国小儿血液与肿瘤杂志》2021年第4期227-232,237,共7页Journal of China Pediatric Blood and Cancer

摘　　要：目的探讨DNA修复相关基因胚系突变所致遗传易感性小儿白血病的诊断思路以及这类疾病临床、遗传学特征。方法收集并回顾性分析2017年5月—2020年1月确诊的5例DNA修复相关基因胚系突变的遗传易感性小儿白血病患儿的临床资料及遗传学、分子学资料。结果伴遗传易感性的白血病患儿中涉及DNA修复缺陷者5例,男2例,女3例。5例中1例TP53突变,2例PMS2突变,1例9p21.3p21.1缺失,1例CHEK2突变。结论白血病诊疗中应注意体貌异常及肿瘤家族史,不存在以上也不能除外肿瘤遗传易感性。需甄别结构性变异,重视基因突变及杂合性缺失两种形式,完全缓解后的拷贝数变异检测应更加积极。TP53c.421T>C p.C141R的胚系突变形式为致病性突变。PMS2的单等位基因突变也可导致典型的结构性错配修复综合征发生。DNA修复缺陷相关胚系突变本身不影响化疗反应,体细胞改变特征才是影响化疗疗效的关键因素。Objective To investigate the clinical and genetic characteristics of pediatric leukemia with hereditary predisposition to cancers due to germline variants associated with DNA repair so as to improve the identification of such cases.Methods The clinical genetic and genomic data of 5 leukemia children with hereditary predisposition to cancers due to germline mutations associated with DNA repair from May 2017 to January 2020 were collected and analyzed retrospectively.Results DNA repair defects were found in five children with leukemia who had hereditary predisposition to cancer.,including 2 males and 3 females,TP53 mutation was found in 1 case,PMS2 mutation were found in 2 cases,9p21.3p21.1 deletion was found in 1 case and CHEK2 mutation was found in 1 case.Conclusions Abnormal physical appearance and family history of tumors play important roles in the diagnosis of leukemia with hereditary predisposition to cancers.However,this diagnosis cannot be ruled out,even without above features.For the identification of constitutional variants,mutations and loss of heterozygosity both need to be detected with different methods,and the copy number variation should be tested more actively after complete remission.Germline mutation of TP53(c.421T>CpC141R)is a pathogenic variant.The monoallelic mutation of PMS2 can produce a typical constitutional mismatch repair deficiency syndrome.Carrying somatic cytogenetic and molecular changes with poor prognosis is the key factor affecting the response to chemotherapy,but not the germline mutation itself.

关 键 词：DNA修复 胚系突变 肿瘤遗传易感性 结构性错配修复缺陷综合征 

分 类 号：R73[医药卫生—肿瘤]