No abstract

The inheritance of mitochondrial haplogroup U is associated with an approximately 2-fold increased risk of prostate cancer and 2.5-fold increased risk of renal cancer in white North American individuals. Therefore, individuals with this mitochondrial haplotype are in a high risk group. Because mitochondrial haplogroup U is found in 9.35% of the white United States population, there are more than 20 million individuals in this high risk group.

Cytogenetic and molecular analysis of DNA sequences with highly polymorphic microsatellite markers have implicated allele loss in several chromosomal regions including 3p, 6p, 6q, 8p, 9p, 9q, 11p and 14q in the pathogenesis of sporadic renal cell carcinomas (RCCs). Deletions involving the long arm of chromosome 7 have not been described in RCCs although they have been seen in several other tumor types. However, there have been no detailed analysis of loss of heterozygosity (LOH) of 7q sequences in sporadic RCCs. We therefore studied LOH for DNA sequences on 7q with 10 highly polymorphic markers in 92 matched normal/tumor samples representing sporadic RCCs including papillary, nonpapillary, and oncocytomas in order to determine whether allelic loss could be detected in a tumor type with no visible 7q rearrangements at the cytogenetic level. We found chromosome 7q allele loss in 59 of 92 cases (64%) involving one, two, or more microsatellite markers. The most common allele loss included loci D7S522 (24%) and D7S649 (30%) at 7q31.1-31.2, a region that contains one of the common fragile sites, FRA7G. By comparative multiplex PCR analysis, we detected a homozygous deletion of one marker in the 7q 31.1-31.2 region in one tumor, RC21. These results support the idea that a tumor suppressor gene in 7q31 is involved in the pathogenesis of sporadic renal cell carcinomas.

The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most active common fragile site in the human genome. We have localized aphidicolininduced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B (Paradee et al., 1996). Sequence analysis of these regions identi®ed two polymorphic microsatellite markers immediately adjacent to each of these breakpoint clusters. In this report we have used these two new microsatellites and 14 additional 3p microsatellites to analyse chromosome 3p breakage and loss in 94 sporadic RCC samples, including nonpapillary, papillary and oncocytomas. We have found heterozygous loss of 3p14 sequences in 460% of the RCC samples, including both clear cell and papillary renal cell carcinomas. We have found frequent breakage in the region immediately surrounding FRA3B, demonstrating that FRA3B does play a role in chromosome breakage and loss in RCC. In contrast to other reports, 450% of the papillary tumors also showed LOH of 3p markers. We also observed microsatellite instability (MIN) with most of the tested markers in seven of eight oncocytomas and one of 69 clear cell carcinomas. The MIN in some oncocytomas was of the RER+ (replication error) type I phenotype. None of the ®ve 3p14.2 markers detected any homozygous deletions in tumor samples, but 69/94 (73%) of the tumors had LOH for the region, which includes the recently identi®ed FHIT gene.

For understanding the structural characteristics and the proteome of Perna shell, the microstructure, polymorph, and protein composition of the adult Perna viridis shell were investigated. The P . viridis shell have two distinct mineral layers, myostracum and nacre, with the same calcium carbonate polymorph of aragonite, determined by scanning electron microscope, Fourier transform infrared spectroscopy, and x-ray crystalline diffraction. Using Illumina sequencing, the mantle transcriptome of P . viridis was investigated and a total of 69,859 unigenes was generated. Using a combined proteomic/transcriptomic approach, a total of 378 shell proteins from P . viridis shell were identified, in which, 132 shell proteins identified with more than two matched unique peptides. Of the 132 shell proteins, 69 are exclusive to the nacre, 12 to the myostracum, and 51 are shared by both. The Myosin-tail domain containing proteins, Filament-like proteins, and Chitin-binding domain containing proteins represent the most abundant molecules. In addition, the shell matrix proteins (SMPs) containing biomineralization-related domains, such as Kunitz, A2M, WAP, EF-hand, PDZ, VWA, Collagen domain, and low complexity regions with abundant certain amino acids, were also identified from P . viridis shell. Collagenase and chitinase degradation can significantly change the morphology of the shell, indicating the important roles of collagen and chitin in the shell formation and the muscle-shell attachment. Our results present for the first time the proteome of P . viridis shell and increase the knowledge of SMPs in this genus.