Representational difference analysis and loss of heterozygosity studies detect 3p deletions in neuroblastoma.

In an attempt to identify genes involved in neuroblastoma, we scanned neuroblastoma tumour DNAs for homozygous deletions by representational difference analysis (RDA). The RDA produced several difference products, nine of which represented hemizygous deletions located on chromosome 1 or 3. In order to detect deletions, a genomewide loss of heterozygosity (LOH) screening with polymorphic markers was performed. Allelic losses on a number of different chromosomes were detected, mainly in favourable neuroblastomas (stage 1, 2 and 4S). The most frequently deleted region, apart from 1p, was chromosomal region 3p. A more detailed study was made in this region, which showed that 9 out of 58 (16%) tested neuroblastoma tumours showed allelic loss in the same region on chromosome 3p, i.e. 3pter-14.2. Thus, both RDA and LOH studies showed chromosome region 3p as being frequently involved in deletions and/or rearrangements in neuroblastoma tumours. Therefore, it is possible that one or more of the 3p genes implicated in the development of other cancers also play a role in neuroblastoma development and/or progression.

Delimitation of a critical tumour suppressor region at distal 1p in neuroblastoma tumours.

We analysed DNA from 68 neuroblastoma tumours for loss of heterozygosity (LOH) on the distal chromosome 1p (1p-LOH) using PCR-based DNA polymorphisms. Fifteen tumours (22%) displayed 1p-LOH. The shortest region of overlap (SRO) for the deletions was defined proximally by marker D1S244 and distally by marker D1S80. The CDC2L1 locus, located on chromosome 1p36, has been put forward as a neuroblastoma tumour suppressor. We analysed coding regions of the CDC2L1 gene in a subset of aggressive neuroblastoma tumours with known allelic loss for different 1p-markers. Single-stranded conformation polymorphism, heteroduplex and sequencing analysis of tumour DNA did not reveal any significant changes in the coding region. Using a DNA sequence polymorphism, we showed, in a primary tumour with an interstitial allelic deletion, that this tumour had both alleles of the CDC2L1 locus retained in the tumour. Thus, we showed that the neuroblastoma tumour suppressor critical region on 1p in our material is defined by loci D1S244 and D1S80 and that the CDC2L1 locus is distal to the critical region.

Analysis of location and integrity of the human PITSLRE (p58(cdc2L1)) genes in neuroblastoma cell genomes.

The family of PITSLRE kinase genes, located in chromosome 1p36, has recently been associated with neuroblastoma tumorigenesis. In order to evaluate the role of these genes as putative tumor suppressor genes, we have analyzed the integrity of the coding region in primary tumors and its location relative to a neuroblastoma consensus deletion. A subset of aggressive neuroblastoma tumors with allelic loss of different parts of chromosome 1p were investigated. Single-strand conformation polymorphism (SSCP), heteroduplex (HD) and sequencing analysis of tumor DNA did not reveal any significant changes in the coding region. In particular, a primary tumor with an interstitial allelic deletion in 1p36 did not reveal concomitant loss of heterozygosity of the PITSLRE gene region when analyzed with a C/T DNA sequence polymorphism in exon 5 of PITSLRE1. FISH analysis on neuroblastoma cell lines with small interstitial deletions and with a balanced translocation in 1p36 revealed that the PITSLRE gene cluster was localized distal to the neuroblastoma consensus deletion. against an involvement of the PITSLRE genes in neuroblastoma tumorigenesis.

Dynamics of Capillary Rise.

An overview and detailed analysis of the classical theory of capillarity is presented. A number of known equations of capillary rise dynamics are shown to be different limiting cases of one rather general equation. Some internal inconsistencies of the classical equations are pointed out. The role of nonlinear dissipation and flow pattern effects in the front zone of the liquid column and near the capillary entrance is discussed. Numerical simulations and experimental data demonstrating some characteristic types of dynamic behavior predicted by the theory are reported. Special attention is paid to the capillary rise of surfactant solutions. As applied to this special case, the existing theory is substantially elaborated by setting up a closed system of equations describing the surfactant transport and relaxation processes in the adsorption layer. A simplified relation for the capillary rise dynamics in the case of strong depletion of the interfacial region is obtained, which is in qualitative agreement with the experimental behavior. Copyright 2000 Academic Press.

Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from, the COL7A1 locus.

Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Zmax = 13.4 at (theta = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus.