The simultaneous and unequivocal discernment of all human chromosomes in different colors would be of significant clinical and biologic importance. Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization. By means of computer separation (classification) of spectra, spectrally overlapping chromosome-specific DNA probes could be resolved, and all human chromosomes were simultaneously identified.
Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low-grade adenomas (n = 14). In high-grade adenomas (n = 12), and overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA-ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF-1 and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high-grade adenomas to invasive carcinomas.
Primary mediastinal (thymic) B-cell lymphoma is a high-grade non- Hodgkin's lymphoma with unique features. By using comparative genomic hybridization and interphase cytogenetics, 26 tumors were analyzed to identify genomic imbalances. Gains of chromosomal material were much more frequent than losses (110 v 10) and involved chromosomes 9p, 12q, and Xq (31% to 50%). Interestingly, gain of Xq coincided with gain of 9p. Distinct high-level amplifications were found in four subregions. In 2 cases, amplifications of proto-oncogene REL were shown by filter hybridization, indicating a possible pathogenic role of this gene. The characteristic pattern of chromosomal imbalances distinct from other B- cell lymphomas suggests a specific pathway of genetic changes associated with this lymphoma.
Comparative genomic hybridization (CGH) allows detection of chromosomal imbalances in whole genomes in a comprehensive manner. With this approach, ten cases of prostate cancer (seven primary tumors and three metastases) were analyzed. Frequent chromosomal gains detected by CGH involved chromosome arms 7q, 8q, 9q, and 16p, and chromosomes 20 and 22, as well as frequent losses of chromosome arms 16q and 18q, in at least three of the ten cases. Overrepresentation of chromosome arm 9q has not been described in published reports. The CGH data were compared with results of a loss of heterozygosity (LOH) study, in which complete allelotyping was performed in the same prostate tumors with 74 different polymorphic markers. In general, a high concordance between the CGH and LOH results was observed (92%). Tumors revealing discrepancies by CGH and LOH analysis were investigated further by interphase cytogenetics, and the resulting picture regarding the genomic alterations is discussed in detail.
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