This review summarizes reports of recurrent DNA sequence copy number losses in human neoplasms detected by comparative genomic hybridization. Recurrent losses that affect each of the chromosome arms in 73 tumor types are tabulated from 169 reports. The tables are available online at http:// www.amjpathol.org and http://www.helsinki.fi/ϳlgl _www/CMG.html. The genes relevant to the lost regions are discussed for each of the chromosomes. The review is supplemented also by a list of known and putative tumor suppressor genes and DNA repair genes (see Table 1 , online). Losses are found in all chromosome arms , but they seem to be relatively rare at 1q , 2p , 3q , 5p , 6p , 7p , 7q , 8q , 12p , and 20q. Losses and their minimal common overlapping areas that were present in a great proportion of the 73 tumor entities reported in Table 2 (see online) are (in descending order of frequency): 9p23-p24 (48%) , 13q21 (47%) , 6q16 (44%) , 6q26-q27 (44%) , 8p23 (37%), 18q22-q23 (37%) , 17p12-p13 (34%) , 1p36.1 (34%), 11q23 (33%) , 1p22 (32%) , 4q32-qter (31%) , 14q22-q23 (25%) , 10q23 (25%) , 10q25-qter (25%) ,15q21 (23%) , 16q22 (23%) , 5q21 (23%) , 3p12-p14 (22%), 22q12 (22%) , Xp21 (21%) , Xq21 (21%) , and 10p12 ( Knowledge of chromosomal deletions has significantly contributed to the detection of tumor suppressor genes, since the inactivation of one allele, according to the twohit hypothesis, often results from a deletion on the chromosomal level.

Cenp-F (mitosin) is a large coiled-coil protein whose function has remained obscure since its identification a decade ago. It has been suggested that the protein plays a role in the kinetochore-mediated mitotic functions but until recently there was little evidence to support this postulation. Recent results from five laboratories have given insights on how Cenp-F may participate in the regulation of cell division. In this mini-review, we will summarize the current data regarding the mitotic tasks of Cenp-F as well as discuss how it is used as a proliferation marker of malignant cell growth in the clinic. Also, the protein's post-translational modification by farnesylation and potential contribution to cell cycle effects of farnesyl transferase inhibitors will be addressed.

Fisetin is a natural flavonol present in edible vegetables, fruits and wine at 2-160 microg/g concentrations and an ingredient in nutritional supplements with much higher concentrations. The compound has been reported to exert anticarcinogenic effects as well as antioxidant and anti-inflammatory activity via its ability to act as an inhibitor of cell proliferation and free radical scavenger, respectively. Our cell-based high-throughput screen for small molecules that override chemically induced mitotic arrest identified fisetin as an antimitotic compound. Fisetin rapidly compromised microtubule drug-induced mitotic block in a proteasome-dependent manner in several human cell lines. Moreover, in unperturbed human cancer cells fisetin caused premature initiation of chromosome segregation and exit from mitosis without normal cytokinesis. To understand the molecular mechanism behind these mitotic errors, we analyzed the consequences of fisetin treatment on the localization and phoshorylation of several mitotic proteins. Aurora B, Bub1, BubR1 and Cenp-F rapidly lost their kinetochore/centromere localization and others became dephosphorylated upon addition of fisetin to the culture medium. Finally, we identified Aurora B kinase as a novel direct target of fisetin. The activity of Aurora B was significantly reduced by fisetin in vitro and in cells, an effect that can explain the observed forced mitotic exit, failure of cytokinesis and decreased cell viability. In conclusion, our data propose that fisetin perturbs spindle checkpoint signaling, which may contribute to the antiproliferative effects of the compound.

DNA copy number amplification at the chromosomal region of 17q is frequent in gastric cancer. Recently 17q21 was identified as the critical region for the amplicon formation because this region harbors the ERBB2 oncogene and several other targets, such as TOP2A and DARPP32. In our study, we characterized the amplification (52 cases) and expression (29 cases) levels of ERBB2, TOP2A and DARPP32 in gastric cancer samples. These 3 genes were concomitantly amplified in 17% of the intestinal type of gastric adenocarcinoma. However, the expression levels were independent, showing overexpression of DARPP32 (48%), TOP2A (17%) and ERBB2 (3%) studied by quantitative real-time PCR. The most frequently overexpressed gene, DARPP32, exhibited strong protein overexpression in 45% (30/66) of the cases in immunohistochemical study of gastric cancer tumor tissue array. Additional studies are required to thoroughly understand the biological significance of these genes in gastric cancer.