Aneuploid colon cancer cells have a robust spindle checkpoint.

Colon cancer cells frequently display minisatellite instability (MIN) or chromosome instability (CIN). While MIN is caused by mismatch repair defects, the lesions responsible for CIN are unknown. The observation that CIN cells fail to undergo mitotic arrest following spindle damage suggested that mutations in spindle checkpoint genes may account for CIN. However, here we show that CIN cells do undergo mitotic arrest in response to spindle damage. Although the maximum mitotic index achieved by CIN lines is diminished relative to MIN lines, CIN cells clearly have a robust spindle checkpoint. Consistently, mutations in spindle checkpoint genes are rare in human tumours. In contrast, the adenomatous polyposis coli (APC) gene is frequently mutated in CIN cells. Significantly, we show here that expression of an APC mutant in MIN cells reduces the mitotic index following spindle damage to a level observed in CIN cells, suggesting that APC dysfunction may contribute to CIN.

Cancer and the web.

The applications of functional genomics, proteomics and informatics to cancer research have yielded a tremendous amount of information, which is growing all the time. Much of this information is available publicly on the Internet and ranges from general information about different cancers from a patient or clinical viewpoint, through to databases suitable for cancer researchers of all backgrounds, to very specific sites dedicated to individual genes or molecules. A simple search for 'cancer' from a typical Web browser search engine yields more than half a million hits; an even more specific search for 'leukaemia' (>40 000 hits) or 'p53' (>5700 hits) yields far too many hits to allow one to identify particular sites of interest. This review aims to provide a brief guide to some of the resources and databases that can be used as springboards to home in rapidly on information relevant to many fields of cancer research. As such, this article will not focus on a single website but hopes to illustrate some of the ways that postgenomic biology is revolutionizing cancer research. It will cover genomics and proteomics approaches that have been applied to studying global expression patterns in cancers, in addition to providing links ranging from general information about cancer to specific cancer gene mutation databases.

Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II beta subunit (CSNK2B).

A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An approximately 220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes, has been analyzed for the presence of additional genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II beta subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product.

Characterization of a novel gene in the human major histocompatibility complex that encodes a potential new member of the I kappa B family of proteins.

At least 110 genes are now known to be located in the 4000 kb of DNA encompassing the human major histocompatibility complex (MHC) in the chromosome band 6p21.3. Recent genomic sequence analysis of a 90 kb segment of DNA containing the tumour necrosis factor genes in the class III region of the MHC has predicted the presence of three potential exons mapping between the BAT1 and TNFB genes (12). A near full-length cDNA clone corresponding to a novel gene located between BAT1 and TNFB that contains sequence corresponding to one of these putative exons, has been isolated from a premonocytic leukaemic cell line cDNA library. Characterization of this gene reveals that it spans 13.5 kb of DNA, with the 3' end of the gene lying approximately 12 kb from the 5' end of the TNFB gene. The cDNA hybridizes to a approximately 1.6 kb mRNA in a number of different cell types, including monocytes, T cells, B cells and hepatocytes. The putative polypeptide encoded by this cDNA is 381 amino acids in length, with a non-glycosylated M(r) of 43214. It contains one partial and two full ANK repeats, which bear a marked similarity to those in the I kappa B family of proteins, suggesting that the protein encoded by the novel gene could represent a divergent member of this family.