While the majority of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases are sporadic, familial MDS/AML cases have also been identified and reported in literature. Inherited mutations in the GATA2, TERC, TERT, CEBPA and RUNX1 genes have been shown to associate with familial MDS/AML (for review see Holme H et al. 2012, Br J Haematol. 158:242-8). Although most of the germline aberrations in these genes are point mutations, deletions have been described as well, e.g. in the GATA2 and RUNX1 genes (Hsu AP et al. 2011, Blood. 118:2653-5, Kazenwadel J et al. 2012, Blood. 119:1283-91, and Liew E and Owen C 2011, Haematologica. 96:1536-42). The most recurrent GATA2 mutations identified in MonoMAC patients are p.R398W (c.1192C>T) and p.T354M (c.1061C>T) (Hsu AP et al. 2011, Blood. 118:2653-5). Furthermore, in the TERT gene the p.A1062T (c.3184G>A) mutation is shown to be a negative prognostic factor in younger AML patients (Both A et al. 2017, Ann Hematol. 96:895-904).
This P437-B1 Familial MDS-AML probemix contains a total of 42 probes for the detection of copy number aberrations in the following genes: GATA2 (at 3q21.3), TERC (at 3q26.2), TERT (at 5p15.33), CEBPA (at 19q13.11) and RUNX1 (at 21q22.12), which are suggested to be of diagnostic relevance in familial MDS/AML. Furthermore, this probemix contains three mutation-specific probes for the GATA2 p.R398W, GATA2 p.T354M and TERT p.A1062T point mutations. In addition, 14 reference probes have been included in this probemix, detecting 13 different autosomal chromosomal locations, which are relatively stable in MDS and AML patient samples.
SD070 Binning DNA
Please note that the mutation-specific probes have only been tested on control plasmids and not on positive human DNA samples with the GATA2 (p.R398W = c.1192C>T and p.T354M = c.1061C>T) and TERT (p.A1062T = c.3184G>A) point mutations! This SD070 Binning DNA is provided with each probemix vial and can be used in data binning in the fragment analysis and as a positive control for the mutation-specific probes (see next page).
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned genes and to detect the presence of the aforementioned point mutations in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in these genes are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.
Sample DNA developed for this product: