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Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes
Author(s) -
Babushok Daria V.,
Xie Hongbo M.,
Roth Jacquelyn J.,
Perdigones Nieves,
Olson Timothy S.,
Cockroft Joshua D.,
Gai Xiaowu,
Perin Juan C.,
Li Yimei,
Paessler Michele E.,
Hakonarson Hakon,
Podsakoff Gregory M.,
Mason Philip J.,
Biegel Jaclyn A.,
Bessler Monica
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12603
Subject(s) - snp array , biology , snp , single nucleotide polymorphism , genetics , loss of heterozygosity , cebpa , medicine , genotype , mutation , allele , gene
Summary The bone marrow failure syndromes ( BMFS ) are a heterogeneous group of rare blood disorders characterized by inadequate haematopoiesis, clonal evolution, and increased risk of leukaemia. Single nucleotide polymorphism arrays ( SNP ‐A) have been proposed as a tool for surveillance of clonal evolution in BMFS . To better understand the natural history of BMFS and to assess the clinical utility of SNP ‐A in these disorders, we analysed 124 SNP ‐A from a comprehensively characterized cohort of 91 patients at our BMFS centre. SNP ‐A were correlated with medical histories, haematopathology, cytogenetic and molecular data. To assess clonal evolution, longitudinal analysis of SNP‐A was performed in 25 patients. We found that acquired copy number‐neutral loss of heterozygosity ( CN ‐ LOH ) was significantly more frequent in acquired aplastic anaemia ( aAA ) than in other BMFS (odds ratio 12·2, P < 0·01). Homozygosity by descent was most common in congenital BMFS , frequently unmasking autosomal recessive mutations. Copy number variants ( CNV s) were frequently polymorphic, and we identified CNV s enriched in neutropenia and aAA . Our results suggest that acquired CN ‐ LOH is a general phenomenon in aAA that is probably mechanistically and prognostically distinct from typical CN ‐ LOH of myeloid malignancies. Our analysis of clinical utility of SNP ‐A shows the highest yield of detecting new clonal haematopoiesis at diagnosis and at relapse.