Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: A phenotype/genotype correlation

Autor: Evelin Schröck, Thomas Ried, Kerstin Heselmeyer-Haddad, Gert Auer, Harald Blegen
Rok vydání: 1999
Předmět:
Zdroj: Genes, Chromosomes and Cancer. 25:195-204
ISSN: 1098-2264
1045-2257
DOI: 10.1002/(sici)1098-2264(199907)25:3<195::aid-gcc1>3.0.co;2-8
Popis: The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low- and high-grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High-level copy number changes (amplifications) become more prevalent in advanced-stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage-specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin-dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage-specific chromosomal aberrations with respect to diagnostic applications. Genes Chromosomes Cancer 25:195–204, 1999. Published 1999 Wiley-Liss, Inc.
Databáze: OpenAIRE
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