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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2022, Vol. 16 Issue (3): 459-466   https://doi.org/10.1007/s11684-021-0841-x
  本期目录
Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies
Daijing Nie1,2, Jing Zhang1, Fang Wang1, Xvxin Li1, Lili Liu1, Wei Zhang1, Panxiang Cao1, Xue Chen1, Yang Zhang1, Jiaqi Chen1, Xiaoli Ma1, Xiaosu Zhou2, Qisheng Wu3, Ming Liu1, Mingyue Liu1, Wenjun Tian4, Hongxing Liu1,2,3()
1. Division of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang 065201, China
2. Beijing Lu Daopei Institute of Hematology, Beijing 100176, China
3. Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital, Beijing 100176, China
4. Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
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Abstract：

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 consulting. We 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 malignancy. Sixty-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.
Key words： Fanconi anemia    aplastic anemia    hematologic malignancy    germline predisposition
收稿日期: 2020-08-06      出版日期: 2022-07-18
Corresponding Author(s): Hongxing Liu   
 引用本文:   
. [J]. Frontiers of Medicine, 2022, 16(3): 459-466.
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. Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies. Front. Med., 2022, 16(3): 459-466.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-021-0841-x
https://academic.hep.com.cn/fmd/CN/Y2022/V16/I3/459
Median age ?(year, range) Sex ratio ?(male/female) Case number
AA 10 (1–63) 1.19 243
MDS 27 (1–65) 1.44 61
AML 14.5 (1–65) 1.34 208
ALL 6 (1–53) 1.38 276
Total 10 (1–65) 1.31 788
Tab.1  
Fig.1  
Gene AA MDS AML ALL ExAC_EAS
?VAF
VAF OR 95% CI P VAF OR 95% CI P VAF OR 95% CI P VAF OR 95% CI P
BRCA2 0.62 0.69 0.22–2.20 0.800 1.64 1.87 0.45–7.80 0.301 1.20 1.36 0.54–3.40 0.426 1.81 2.08 1.06–4.06 0.038 0.89
FANCA 1.85 2.41 1.19–4.89 0.020 2.46 3.24 0.99–10.59 0.075 2.16 2.83 1.39–5.76 0.008 1.45 1.87 0.89–3.93 0.135 0.78
FANCC 0.62 1.79 0.54–5.91 0.255 0.82 2.39 0.32–17.79 0.353 0.48 1.39 0.33–5.86 0.657 0.18 0.52 0.07–3.83 1.000 0.35
FANCD2 0.62 0.76 0.24–2.43 1.000 0.82 1.01 0.14–7.42 1.000 0.48 0.59 0.14–2.42 0.773 0.54 0.67 0.21–2.14 0.801 0.81
FANCG 0.21 0.71 0.10–5.27 1.000 0 – – 1.000 0.24 0.83 0.11–6.16 1.000 0.18 0.63 0.08–4.64 1.000 0.29
Total 3.91 1.20 0.73–1.97 0.496 5.74 1.64 0.70–3.84 0.278 4.57 1.51 0.93–2.46 0.108 4.17 1.37 0.88–2.13 0.163 3.12
Tab.2  
Fig.2  
Fig.3  
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