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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies / 医学前沿
Frontiers of Medicine ; (4): 459-466, 2022.
Article in English | WPRIM | ID: wpr-939879
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Leukemia, Myeloid, Acute / Retrospective Studies / Hematologic Neoplasms / Epigenesis, Genetic / Fanconi Anemia / Germ Cells / Anemia, Aplastic Type of study: Observational study Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Leukemia, Myeloid, Acute / Retrospective Studies / Hematologic Neoplasms / Epigenesis, Genetic / Fanconi Anemia / Germ Cells / Anemia, Aplastic Type of study: Observational study Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2022 Type: Article