Prognostic microRNA expression signature from examination of colorectal primary and metastatic tumors.

While previous studies have described associations between specific microRNAs and colorectal cancer (CRC) metastasis, our understanding of microRNA regulation of metastatic spread remains largely unexplored. To identify microRNAs critical for disease progression, we measured microRNA expression in primary CRC tumors and synchronous liver metastases in 19 cases using quantitative polymerase chain reaction (qPCR) arrays. We identified 16 microRNAs significantly differentially expressed between primary tumors and liver metastases that distinguish primary tumors and liver metastases by hierarchical clustering. Combinations of microRNAs expressed in the primary tumor and in the metastatic tumor are associated with survival, but these signatures have no microRNAs in common. We found that increased expression of miR-210 and miR-133b in liver metastases compared to primary tumors is associated with lower survival. We propose that evaluating the change in expression between primary and metastatic tumors in each patient may lead to improved biomarker development.

A case report and review of transitional cell carcinoma in children.

Transitional cell carcinoma (TCC) is a rare cause of hematuria in children. This type of urothelial bladder tumor is typically low grade and carries a good prognosis. In this article, a case report is presented along with a review of the literature on TCC in children.

RNAi and heterochromatin repress centromeric meiotic recombination.

During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes, is essential in most species for proper homologue segregation. Nevertheless, recombination is repressed specifically in and around the centromeres of chromosomes, apparently because rare centromeric (or pericentromeric) recombination events, when they do occur, can disrupt proper segregation and lead to genetic disabilities, including birth defects. The basis by which centromeric meiotic recombination is repressed has been largely unknown. We report here that, in fission yeast, RNAi functions and Clr4-Rik1 (histone H3 lysine 9 methyltransferase) are required for repression of centromeric recombination. Surprisingly, one mutant derepressed for recombination in the heterochromatic mating-type region during meiosis and several mutants derepressed for centromeric gene expression during mitotic growth are not derepressed for centromeric recombination during meiosis. These results reveal a complex relation between types of repression by heterochromatin. Our results also reveal a previously undemonstrated role for RNAi and heterochromatin in the repression of meiotic centromeric recombination and, potentially, in the prevention of birth defects by maintenance of proper chromosome segregation during meiosis.

A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events.

Meiosis is a specialized form of cell division by which sexually reproducing diploid organisms generate haploid gametes. During a long prophase, telomeres cluster into the bouquet configuration to aid chromosome pairing, and DNA replication is followed by high levels of recombination between homologous chromosomes (homologs). This recombination is important for the reductional segregation of homologs at the first meiotic division; without further replication, a second meiotic division yields haploid nuclei. In the fission yeast Schizosaccharomyces pombe, we have deleted 175 meiotically upregulated genes and found seven genes not previously reported to be critical for meiotic events. Three mutants (rec24, rec25, and rec27) had strongly reduced meiosis-specific DNA double-strand breakage and recombination. One mutant (tht2) was deficient in karyogamy, and two (bqt1 and bqt2) were deficient in telomere clustering, explaining their defects in recombination and segregation. The moa1 mutant was delayed in premeiotic S phase progression and nuclear divisions. Further analysis of these mutants will help elucidate the complex machinery governing the special behavior of meiotic chromosomes.

Cohesins are required for meiotic DNA breakage and recombination in Schizosaccharomyces pombe.

In preparation for the unique segregation of homologs at the first meiotic division, chromosomes undergo dramatic changes. The meiosis-specific sister chromatid cohesins Rec8 and Rec11 of Schizosaccharomyces pombe are recruited around the time of premeiotic replication, and Rec10, a component of meiosis-specific linear elements, is subsequently added. Here we report that Rec10 is essential for meiosis-specific DNA breakage by Rec12 (Spo11 homolog) and for meiotic recombination. DNA breakage and recombination also depend on the Rec8 and Rec11 cohesins, strictly in some genomic intervals but less so in others. Thus, in addition to their previously recognized role in meiotic chromosome segregation, cohesins have a direct role, as do linear element components, in meiotic recombination by enabling double-strand DNA break formation by Rec12. Our results reveal a pathway, whose regulation is significantly different from that in the distantly related yeast Saccharomyces cerevisiae, for meiosis-specific chromosome differentiation and high-frequency recombination.

Swi5 acts in meiotic DNA joint molecule formation in Schizosaccharomyces pombe.

Previously isolated Schizosaccharomyces pombe swi5 mutants are defective in mitotic mating-type switching and in repair of meiotic recombination-related DNA double-strand breaks. Here, we identify the swi5 gene, which encodes an 85-amino-acid polypeptide, similar to Sae3 of Saccharomyces cerevisiae, with an N-terminal predicted coiled-coil domain. A swi5 complete deletion mutant had normal mitotic growth rate but was hypersensitive to DNA-damaging agents and defective in mating-type switching. In meiosis, recombinant frequencies were reduced by a factor of approximately 10. The swi5 deletion strongly reduced the viable spore yields of mutants lacking Rhp55 or Rhp57, proteins thought to aid joint molecule formation. Furthermore, the swi5 deletion strongly suppressed the low viable spore yield of mutants lacking Mus81*Eme1, which resolves joint molecules such as Holliday junctions. These and previous results indicate that the small Swi5 polypeptide acts in a branched pathway of joint molecule formation to repair meiotic DNA breaks.