Recurrent genetic defects on chromosome 7q in myeloid neoplasms.
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ABSTRACT:
SUBMITTER: Hosono N
PROVIDER: S-EPMC8694066 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Publications
Recurrent genetic defects on chromosome 7q in myeloid neoplasms.
Hosono N N Makishima H H Jerez A A Yoshida K K Przychodzen B B McMahon S S Shiraishi Y Y Chiba K K Tanaka H H Miyano S S Sanada M M Gómez-Seguí I I Verma A K AK McDevitt M A MA Sekeres M A MA Ogawa S S Maciejewski J P JP
Leukemia 20140116 6
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Project description:BackgroundDeletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms.Materials and methodsTo define the pathogenic molecular features associated with del(5q), next-generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5.FindingsA number of 5q genes with haploinsufficient expression and/or recurrent somatic mutations were identified; for these genes, CSNK1A1 and G3BP1 within the commonly deleted 5q region and DDX41 within a commonly retained region were most commonly affected by somatic mutations. These genes showed consistent haploinsufficiency in deleted cases; low expression/mutations of G3BP1 or DDX41 were associated with poor survival, likely due to decreased cellular function. The most common mutations on other chromosomes in patients with del(5q) included TP53, and mutations of FLT3 (ITD or TKD), NPM1 or TET2 and were mutually exclusive. Serial sequencing allowed for definition of clonal architecture and dynamics, in patients with exome sequencing allelic imbalance for informative SNPs facilitated simultaneous approximation of clonal size of del(5q) and clonal burden for somatic mutations.InterpretationOur results illuminate the spectrum of molecular defects characteristic of del(5q), their clinical impact and succession of stepwise evolution.
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Project description:BackgroundAn interstitial deletion of the long arms of chromosome 20, del(20)(q), is frequent in the bone marrow (BM) of patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), and it is recurrent in the BM of patients with Shwachman-Diamond syndrome (SDS), who have a 30-40% risk of developing MDS and AML.ResultsWe report the results obtained by microarray-based comparative genomic hybridization (a-CGH) in six patients with SDS, and we compare the loss of chromosome 20 material with one patient with MDS, and with data on 92 informative patients with MDS/AML/MPN and del(20)(q) collected from the literature.ConclusionsThe chromosome material lost in MDS/AML/MPN is highly variable with no identifiable common deleted regions, whereas in SDS the loss is more uniform: in 3/6 patients it was almost identical, and the breakpoints that we defined are probably common to most patients from the literature. In some SDS patients less material may be lost, due to different distal breakpoints, but the proximal breakpoint is in the same region, always leading to the loss of the EIF6 gene, an event which was related to a lower risk of MDS/AML in comparison with other patients.
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