Demonstration of acquired hemizygosity and clonality in acute lymphoblastic leukemia with chromosome 7 abnormalities using hypervariable DNA probes

Abstract

Clonal abnormalities of chromosome(s) 7 were investigated in two patients with acute lymphoblastic leukemia. The abnormal karyotypes were 46,XY,-7,del(6)(q13q21), + i(7q)/47,XY,del(6), + i(7q) in case 1, and 46,XX,-7,t(4;11)(q21;q23), + i(7q) in case 2. DNA from leukemic tissue was investigated with Southern blotting using hypervariable DNA probes lambda MS31 and p lambda g3 located on 7p and 7q, respectively. Restriction fragment length polymorphisms (RFLPs) were detected on the short arm in case 1 and on both arms in case 2, and a marked difference in intensity between the two alleles was observed. In case 1 the acquired hemizygosity of 7p, suggested by the cytogenetic findings, was confirmed by Southern blotting. Thus, one chromosome 7 formed the i(7q) and the other No. 7 was duplicated. In case 2 the results of the Southern blotting indicated that the size of the clone with i(7q) was considerably greater than suggested by cytogenetic analysis of the few available metaphase cells.

Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22

“…Localization of KRIT1 to 7q21-22 is particularly interesting, in that 7q22 has been frequently implicated as a site of chromosomal alterations in a variety of cancers, including myeloid disorders and uterine leiomyomata (Kere et al, 1987;Luna-Fineman et al, 1995;Ogata et al, 1993;Pedersen-Bjergaard et al, 1982;Sargent et al, 1994;Weiss et al, 1987;Yamada et al, 1990). While a role for Krev-1/rap1A has not been investigated in these classes of malignancies, a characteristic feature of chromosome 7 monosomy and 7q22 deletions is their occurrence as secondary events following hyperactivation of Ras or mutation of the Ras-GAP protein neuro®bromatosis 1 (NF-1) gene (Ballester et al, 1990;Martin et al, 1990;Xu et al, 1990;reviewed in Luna-Fineman et al, 1995).…”

Formation of a hyperdiploid karyotype in childhood acute lymphoblastic leukemia [see comments]

“…When quantifying the intensity of bands for VNTR (variable number of tandem repeats) probes, a mathematical correction was made. 14 The intensity of lower bands in the autoradiogram were corrected by the following formula: lower band intensity x upper band size/lower band size.…”