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Shwachman‐Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability
Author(s) -
Valli Roberto,
Minelli Antonella,
Galbiati Marta,
D'Amico Giovanna,
Frattini Annalisa,
Montalbano Giuseppe,
Khan Abdul W.,
Porta Giovanni,
Millefanti Giorgia,
Olivieri Carla,
Cipolli Marco,
Cesaro Simone,
Pasquali Francesco,
Danesino Cesare,
Cazzaniga Gianni,
Maserati Emanuela
Publication year - 2019
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.15729
Subject(s) - bone marrow , genome instability , chromosome , medicine , pathology , chromosome instability , diamond–blackfan anemia , somatic evolution in cancer , long arm , bone marrow failure , cancer research , immunology , biology , stem cell , genetics , haematopoiesis , dna , gene , dna damage , ribosome , rna
Summary In Shwachman‐Diamond syndrome ( SDS ), deletion of the long arm of chromosome 20, del(20)(q), often acquired in bone marrow ( BM ), may imply a lower risk of developing myelodysplastic syndrome/acute myeloid leukaemia ( MDS / AML ), due to the loss of the EIF 6 gene. The genes L3 MBTL 1 and SGK 2 , also on chromosome 20, are in a cluster of imprinted genes, and their loss implies dysregulation of BM function. We report here the results of array comparative genomic hybridization (a‐ CGH ) performed on BM DNA of six patients which confirmed the consistent loss of EIF 6 gene. Interestingly, array single nucleotide polymorphisms ( SNP s) showed copy neutral loss of heterozygosity for EIF 6 region in cases without del(20)(q). No preferential parental origin of the deleted chromosome 20 was detected by microsatellite analysis in six SDS patients. Our patients showed a very mild haematological condition, and none evolved into BM aplasia or MDS / AML . We extend the benign prognostic significance of del(20)(q) and loss of EIF 6 to the haematological features of these patients, consistently characterized by mild hypoplastic BM , no or mild neutropenia, anaemia and thrombocytopenia. Some odd results obtained in microsatellite and SNP ‐array analysis demonstrate a peculiar genomic instability, in an attempt to improve BM function through the acquisition of the del(20)(q).