at Chromosome 7 Carry Distinct Biologic and Prognostic Implications in Myelodysplast ic/Myeloprolifer ative Syndromes and Related Marrow Failures

Deletions involving chromosome 7 are frequently encountered in myeloid malignancies, mostly imparting a poor prognosis. Single nucleotide polymorphism array (SNP-A)-based cytogenetics has allowed for an improvement in the mapping of disease-related chromosomal regions through identification of microdeletion that define minimally affected areas for the search for pathogenic mutations. In addition, SNP-A facilitated the detection of somatic uniparental disomy (sUPD), which is frequently found in myeloid malignancies. Regions of sUPD are often associated with homozygous mutations present in the affected area, as shown for example for UPD9p and JAK2 or UPD11q and C-CBL mutations. Based on the precise mapping of genomic lesions on chromosome 7, we compared the outcomes of patients characterized by specific chromosomal abnormalities. Among 1163 patients with various myeloid malignancies studied by SNP-A we identified patients with somatic LOH involving chromosome 7 for whom clinical outcome data was available to assess survival. Regions fulfilling the criteria of germ line-encoded copy number variants and regions of homozygosity present in a control cohort (N=1535) were excluded. The rest of newly observed regions were in/excluded based on their absence or presence in the paired non-clonal DNA. In total, we identified 45 patients with monosomy 7, 37 patients with del(7q), and 21 with UPD7q. The CDR for del(7q) and UPD(7q) spanned nt 115221516-126602492 and nt 127,484,450-158821424, respectively. Among patients with monosomy 7, 17 were primary MDS, 22 had various bone marrow failure disorders including juvenile myelomonocytic leukemia (JMML) and clonal disease in the context of aplastic anemia (AA) and Fanconi anemia (FA), whereas UPD7q was predominantly found in MDS/MPD and MPD (N=10), sAML (N=3), and primary MDS (N=7). Patients with del(7q) included primary MDS and sAML. The most common