Chromosome 7 long arm deletion in myeloid disorders: a narrow breakpoint region in 7q22 defined by molecular mapping

Abstract

The involvement of the erythropoietin (EPO), plasminogen activator inhibitor type I (PAI1), and multi-drug resistance (MDR2) genes located in chromosomal region 7q21–22 was studied in patients with myeloid disorders and with or without a chromosome 7 abnormality. Separated blood mononuclear cells and granulocytes from 21 patients were used in restriction fragment length polymorphism (RFLP) studies with gene- specific DNA probes. A marked weakness of one of the allelic bands was observed in granulocyte-derived DNA from heterozygous patients with monosomy 7. In four patients with a partial deletion of chromosome 7 long arm (7q-), marked weakness of an allelic band was observed in granulocyte-derived DNA with PAI1 probe (four heterozygous patients) and MDR2 probe (one heterozygous patient), implying deletion of these genes. In contrast, the EPO gene was not deleted in these patients, as demonstrated by the presence of two allelic bands of equal strength in granulocyte-derived DNA (two patients) or by gene dosage estimation (two patients). Two allelic bands of equal strength were also observed in three heterozygous patients with an arbitrary probe (pKV13) located in 7cen-q21.3. Unexpected hemizygosity or hybridization bands were not observed in any patient. We conclude that PAI1 and MDR2 are located distally of EPO in 7q22, and that none of these genes is commonly rearranged in myeloid disorders. The chromosome 7 long arm deletion breakpoint is located in a relatively narrow segment between the PAI1 and EPO genes in different patients. The deletion may involve a specific site in DNA, since the genetic distance between the PAI1 and EPO genes is only 3 cM.

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas

“…The precise mapping of the deletion on 7q has been reported as an interstitial deletion of the distal portion of 7q in leukemia cells. The proximal breakpoint of the interstitial deletion is determined at 7q22 (Kere et al, 1989). In the present study, gastric carcinomas showed no deletion a t D7S64 (7q21), in contrast to frequent LOH at the c-met locus (7q31).…”

“…In the present study, several cases showed wide ranges of LOH at the neighboring 2 to 4 loci. Previous cytogenetic studies have demonstrated the deletion on 7q in gastric carcinomas (Xiao et al, 1992;Ochi et al, 1986), esophageal carcinomas (Xiao et al, 1991) and hematological malignancy (Kere et al, 1989;Michalovaet al, 1991). The precise mapping of the deletion on 7q has been reported as an interstitial deletion of the distal portion of 7q in leukemia cells.…”

Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor Loci

“…Although L O H has been found for several markers on 7q (e.g., Kere et al, 1987aKere et al, ,b, 1989aNeuman et al, 1992), no gene with a putative tumor suppressor function has been detected as yet. T h e molecular studies have, on the other hand, provided further support for the sensitivity of cytogenetic analyses in detecting genetic loss; L O H is rare without cytogenetically detectable 7q deletions (Kere et al, 1989b;Neuman et al, 1992), although exceptions exist (Abrahamson et al, 1993).…”

Molecular delineation of the commonly deleted segment in mature B-cell lymphoid neoplasias with deletion of 7q

“…A large series of YAC clones has been mapped to chromosome 7 (Green et al, 1994(Green et al, , 1995Kunz et al, 1994). Previous reports, using a molecular cytogenetic approach, located the upper breakpoint of the del(7) in myeloid disorders to a segment between the PAI1 and EPO genes (Kere et al, 1989). Delineation of breakpoints at the subchromosomal level in deleted chromosomes 7 in lymphoid disorders has not been reported.…”