Chromosome 3p deletions in head and neck carcinomas: statistical ascertainment of allelic loss.

Loss of function of tumor suppressor genes is important in the origin and progression of common adult tumors. Loss of heterozygosity indicating allelic loss has been used to detect chromosomal regions that harbor these genes. Using over 20 restriction fragment length polymorphism markers spaced throughout the entire length of chromosome 3p, we have generated 3p allelotypes for 18-26 head and neck squamous cell carcinoma cell lines. We then estimated the average heterozygosity over 19 loci for a random sample drawn from natural populations to be 7.80 and that for the tumor lines to be 1.65, indicating a gross reduction of heterozygosity, presumably due to allelic loss. Further comparison of per locus heterozygosity in normal and tumor DNAs showed which loci contributed to the general loss of heterozygosity. We showed that the commonly deleted region of 3p probably lies telomeric to D3S3 (3p14) and centromeric to RAF1 (3p25). This large region includes several putative tumor suppressor genes involved in multiple common tumor types of lung, breast, kidney, ovary, and cervix. The data demonstrate that chromosome 3p allelic loss is a common event in head and neck cancers and suggest that chromosome 3p tumor suppressor genes contribute to the pathogenesis of these tumors.

Metal Iodate-Based Energetic Composites and Their Combustion and Biocidal Performance.

The biological agents that can be weaponized, such as Bacillus anthracis, pose a considerable potential public threat. Bacterial spores, in particular, are highly stress resistant and cannot be completely neutralized by common bactericides. This paper reports on synthesis of metal iodate-based aluminized electrospray-assembled nanocomposites which neutralize spores through a combined thermal and chemical mechanism. Here metal iodates (Bi(IO3)3, Cu(IO3)2, and Fe(IO3)3) act as a strong oxidizer to nanoaluminum to yield a very exothermic and violent reaction, and simultaneously generate iodine as a long-lived bactericide. These microparticle-assembled nanocomposites when characterized in terms of reaction times and temporal pressure release show significantly improved reactivity. Furthermore, sporicidal performance superior to conventional metal-oxide-based thermites clearly shows the advantages of combining both a thermal and biocidal mechanism in spore neutralization.

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.

A genetic linkage map of 96 loci on the short arm of human chromosome 3.

We constructed a genetic map of 96 loci on the short arm of human chromosome 3 (3p) in 59 families provided by the Centre d'Etude du Polymorphisme Humaine (CEPH). Twenty-nine continuously linked loci were placed on the map with likelihood support of at least 1000:1; one locus, D3S213, was placed on the map with likelihood support of 871:1; D3Z1, an alpha satellite centromeric repeat probe, was placed on the map with likelihood support of 159:1; 65 loci were assigned regional locations. The average heterozygosity of the uniquely ordered markers was 49%. The map extends from 3p26, the terminal band of 3p, to the centromere (from D3S211 to D3Z1). Multipoint linkage analysis indicated that the male, female, and sex-averaged maps extend for 102, 147, and 116 cM, respectively. The mean genetic distance between uniquely ordered loci on the sex-averaged map was 4.0 cM. Probe density was greatest for the region of 3p between D3F15S2e and the telomere. The sex-averaged map contained two intervals greater than 10 cM. Seventeen probes were localized by fluorescence in situ hybridization. The loci described in this report will be useful in building an integrated genetic and physical map of this chromosome.