Adjuvant treatment with docetaxel, as compared with vinorelbine, improves recurrence-free survival in women with early breast cancer. A short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER2/neu gene. (International Standard Randomised Controlled Trial number, ISRCTN76560285.).

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.

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Summary Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1 q.

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited condition characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation.

Little is known about the genomic alterations underlying osteosarcoma. We performed a genomewide high-resolution gene copy number analysis of 22 osteosarcoma samples using comparative genomic hybridization on a cDNA microarray that contained cDNA clones of about 13,000 genes. Nineteen of the 22 cases had amplifications that on average spanned more than 1 Mb and contained more than 10 genes. Numerous regions of gain and loss were identified, and their boundaries were defined at high resolution. Novel amplicons were found at 14q11, 17q25, and 22q11-q13. Earlier-known large amplified regions were detected at 12q11-q15, 8q24, 6p12-p13, and 17p11-p13 in 8, 6, 5, and 4 of the 22 samples, respectively. Amplification of 12q was observed more frequently (36% of the cases) than previously reported. Previously known small amplicons at 1p34-p36, 1q21, 19q13, and 21q22 were seen in at least three cases. Our results implicate TOM1L2 and CYP27B1 as having roles as novel targets for the 17p and 12q amplicons, respectively. Details (www.helsinki.fi/cmg) of the amplified genes in each amplicon provide valuable raw data for further in silico studies.

Although greater than 50% of Ewing tumours contain non-random cytogenetic aberrations in addition to the pathognomonic 22q12 rearrangements, little is known about their prognostic significance. To address this question, tumour samples from 134 Ewing tumour patients were analysed using a combination of classical cytogenetics, comparative genomic and fluorescence in situ hybridisation. The evaluation of the compiled data revealed that gain of chromosome 8 occurred in 52% of Ewing tumours but was not a predictive factor for outcome. Gain of 1q was associated with adverse overall survival and event-free survival in all patients, irrespective of whether the tumour was localised or disseminated (overall survival: P=0.002 and P=0.029; eventfree survival: P=0.018 and P=0.010). Loss of 16q was a significant predictive factor for adverse overall survival in all patients (P=0.008) and was associated with disseminated disease at diagnosis (P=0.039). Gain of chromosome 12 was associated with adverse event-free survival (P=0.009) in patients with localised disease. These results indicate that in addition to a 22q12 rearrangement confirmation in Ewing tumours it is important to assess the copy number of 1q and 16q to identify patients with a higher probability of adverse outcome.

It has been proposed that human tumors contain stem cells that have a central role in tumor initiation and posttreatment relapse. Putative breast cancer stem cells may reside in the CD44 + CD24