Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

作     者：Daijing Nie Jing Zhang Fang Wang Xvxin Li Lili Liu Wei Zhang Panxiang Cao Xue Chen Yang Zhang Jiaqi Chen Xiaoli Ma Xiaosu Zhou Qisheng Wu Ming Liu Mingyue Liu Wenjun Tian Hongxing Liu Daijing Nie;Jing Zhang;Fang Wang;Xvxin Li;Lili Liu;Wei Zhang;Panxiang Cao;Xue Chen;Yang Zhang;Jiaqi Chen;Xiaoli Ma;Xiaosu Zhou;Qisheng Wu;Ming Liu;Mingyue Liu;Wenjun Tian;Hongxing Liu

作者机构：Division of Laboratory MedicineHebei Yanda Lu Daopei HospitalLangfang 065201China Beijing Lu Daopei Institute of HematologyBeijing 100176China Division of Pathology&Laboratory MedicineBeijing Lu Daopei HospitalBeijing 100176China Department of Clinical Laboratory MedicineShandong Provincial Hospital Affiliated to Shandong UniversityJinan 250021China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2022年第16卷第3期

页      面：459-466页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by a grant from the Shandong Nature Science Fund(No.ZR2016HP02) 

主　　题：Fanconi anemia aplastic anemia hematologic malignancy germline predisposition 

摘      要：Whether Fanconi anemia(FA)heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family *** retrospectively analyzed rare possibly significant variations(PSVs)in the five most obligated FA genes,BRCA2,FANCA,FANCC,FANCD2,and FANCG,in 788 patients with aplastic anemia(AA)and hematologic ***-eight variants were identified in 66 patients(8.38%).FANCA was the most frequently mutated gene(n=29),followed by BRCA2(n=20).Compared with that of the ExAC East Asian dataset,the overall frequency of rare PSVs was higher in our cohort(P=0.016).BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia(P=0.038),and FANCA PSVs were significantly enriched in AA and AML subgroups(P=0.020;P=0.008).FA-PSV-positive MDS/AML patients had a higher tumor mutation burden,higher rate of cytogenetic abnormalities,less epigenetic regulation,and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients(P=0.024,P=0.029,P=0.024,and P=0.013).The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.