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Biomedical subjects

M I Lerman

Publications and source records attributed to M I Lerman.

At least 127 records · Page 7Linked to original sources
PubMed1991

Molecular analysis of genetic changes in the origin and development of renal cell carcinoma.

Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 which suggests the presence of a tumor suppressor gene at this location. In order to more precisely define the location of the renal cell carcinoma gene and to differentiate molecular changes occurring in early stages of renal neoplasia versus those occurring later in malignant progression, DNA from normal and tumor tissue from 60 patients with various stages of renal cell carcinoma was analyzed for loss of alleles at different chromosomal loci. In tumor tissue from 51 of 58 evaluable patients (88%) there was loss of heterozygosity at one or more of 10 loci tested on chromosome 3 independently of tumor stage. Analysis of the genotypes identified the distal portion of 3p bounded by D3S2 and D3S22 (3p21-26) as the region of the disease gene. In tumor tissue from patients with advanced renal cell carcinoma, we found loss of heterozygosity on chromosome 11p in 5 of 21 (24%), on chromosome 13 in 3 of 9 (33%), and on chromosome 17 in 2 of 19 (11%). We found no loss of heterozygosity at the loci on chromosomes 11, 13, or 17 in tumor tissue from patients with localized renal cell carcinoma (N = 5). These data suggest the existence of a tumor suppressor gene on chromosome 3p which may be essential to the genesis of sporadic renal cell carcinoma and that other tumor suppressor genes are associated with progression of this malignancy.

Adult↗
PubMed1991

Isolation and regional localization of a large collection (2,000) of single-copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes.

A collection of 2,000 lambda phage-carrying human single-copy inserts (greater than 700 bp) were isolated from two chromosome-3 flow-sorted libraries. The single-copy DNA fragments were first sorted into 3p and 3q locations and about 700 3p fragments were regionally mapped using a deletion mapping panel comprised of two human-hamster and two-human-mouse cell hybrids, each containing a chromosome 3 with different deletions in the short arm. The hybrids were extensively mapped with a set of standard 3p markers physically localized or ordered by linkage. The deletion mapping panel divided the short arm into five distinct subregions (A-E). The 3p fragments were distributed on 3p regions as follows: region A, 26%; B, 31%; C, 4%; D, 4% and E, 35%. We screened 300 single-copy DNA fragments from the distal part of 3p (regions A and B) with ten restriction endonucleases for their ability to detect restriction fragment length polymorphisms (RFLPs). Of these fragments 110 (36%) were found to detect useful RFLPs; 35% detected polymorphisms with frequency of heterozygosity of 40% or higher, and 25% with frequency of 30% or higher. All polymorphisms originated from single loci and most of them were of the base pair substitution type. These RFLP markers make it possible to construct a fine linkage map that will span the distal part of chromosome 3p and encompasses the von Hippel-Lindau disease locus. The large number of single-copy fragments (2,000) spaced every 100-150 kb on chromosome 3 will make a significant contribution to mapping and sequencing the entire chromosome 3. The 300 conserved chromosome 3 probes will increase the existing knowledge of man-mouse homologies.

Animals↗