Molecular Cytogenetic Characterization of a Critical Region in Bands 7q35-q36 Commonly Deleted in Malignant Myeloid Disorders

Abstract

Loss of chromosome 7 (؊7) or deletion of the long arm (7q؊) are recurring chromosome abnormalities in myeloid leukemias. The association of ؊7/7q؊ with myeloid leukemia suggests that these regions contain novel tumor suppressor gene(s), whose loss of function contribute to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified, one in band q22 and another in bands q32-q35. Presently there are no data available on the molecular delineation of the distal critical region. In this study we analyzed bone marrow and blood samples from 13 patients with myeloid leukemia (de novo myelodysplastic syndrome [MDS] , n ‫؍‬ 3; de novo acute myeloid leukemia [AML], n ‫؍‬ 9; therapyrelated (t-) AML, n ‫؍‬ 1) which, on chromosome banding analysis, exhibited deletions (n ‫؍‬ 12) or in one case a balanced translocation involving bands 7q31-qter using fluorescence in situ hybridization (FISH). As probes we used representative clones from a contig map of yeast artificial chromosome (YAC) clones that spans chromosome bands 7q31.1-qter. In the 12 cases with loss of 7q material, we identified a commonly deleted region of approximately 4 to 5 megabasepairs in size encompassing the distal part of 7q35 and the proximal part of 7q36. Furthermore, the breakpoint of the reciprocal translocation from the patient with t-AML was localized to a 1,300-kb sized YAC clone that maps to the proximal boundary of the commonly deleted region. Interestingly, in this case both homologs of chromosome 7 were affected: one was lost (؊7) and the second exhibited the t(7q35). The identification and delineation of translocation and deletion breakpoints provides the first step toward the identification of the gene(s) involved in the pathogenesis of 7q35-q36 aberrations in myeloid disorders.

hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

“…11 Interestingly, the hIan gene family is located within a region of chromosome 7q36.1 that is deleted in a subgroup of AML patients. 17 In addition, chromosomal gains on chromosome 7q are recurrent aberrations in follicular lymphomas, which is in keeping with our finding that hIan5 is upregulated in B-cell lymphoid malignancies.…”

“…The murine, rat and human Ian family members have recently been compiled by MacMurray et al 9 A search of the Online Mendelian Inheritance in Man database revealed no obvious disease candidates associated with the hIan5 gene on chromosome 7q36.1, but the gene lies within a critical region deleted in a subgroup of acute myeloid leukemia (AML) patients with 7q35-36 deletion. 17 HIan5 consists of three exons including a first noncoding 5 0 exon, a short coding second exon (first 14 amino acids) and a large third coding exon. Similar to the rat, there may be a long isoform of hIan5 (FlJ31006).…”

Cloning of B cell lymphoma-associated antigens using modified phage-displayed expression cDNA library and immunized patient sera

“…The translated fragment of FL-aa-7 corresponded to an alternative reading frame of hGIMAP7 of the locus such as TCRγ alternative reading frame protein (TARP) (Wolfgang et al, 2000). The fact that leukemia cells often contain deletions or translocation breakpoints within a region on chromosome 7q35-7q36.1 that also contains the hGIMAP gene cluster (Dohner et al, 1998), suggests that the FL-aa-7 peptide might be a product of chromosomal rearrangement with genes such as low density lipid receptor (LDLR) (Wang et al, 1999), although it is derived from an unknown gene, expressed specifically by follicular B cell lymphomas.…”

Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype

“…These abnormalities were previously shown to have prognostic significance accounting for approximately 25% of chromosome anomalies in all MDS patients. 4,19,[27][28][29][30][31][32] Our analysis showed that 17.8% of the patients with normal karyotype presented some of these chromosomal abnormalities in 15-32% of the cells when analyzed by FISH. The most frequent FISH numerical abnormality was represented by trisomy 8 which was detected in the 33.3% of these patients.…”