1. Molecular evolution of multiple recurrent cancers of the bladder
- Author
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Angela A.G. van Tilborg, Ellen C. Zwarthoff, Annie de Vries, Lilian E. Groenfeld, Theo H. van der Kwast, and Maarten de Bont
- Subjects
Mitotic crossover ,Genotype ,Loss of Heterozygosity ,Biology ,medicine.disease_cause ,Evolution, Molecular ,Molecular evolution ,Bladder Neoplasm ,Genetics ,medicine ,Humans ,Receptor, Fibroblast Growth Factor, Type 3 ,Molecular Biology ,Phylogeny ,Genetics (clinical) ,Urinary bladder ,Bladder cancer ,General Medicine ,Protein-Tyrosine Kinases ,medicine.disease ,Receptors, Fibroblast Growth Factor ,Pedigree ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Genetic marker ,Tumor progression ,Cancer research ,Neoplasm Recurrence, Local ,Carcinogenesis ,Microsatellite Repeats - Abstract
We describe the reconstruction of bladder tumor development in individual patients spanning periods of up to 17 years. Genomic alterations detected in the tumors were used for hierarchical cluster analysis of tumor subclones. The cluster analysis highlights the clonal relationship between tumors from each patient. Based on the cluster data we were able to reconstruct the evolution of tumors in a genetic tree, where tumors with few aberrations precede those with many genetic insults. The sequential order of the tumors in these pedigrees differs from the chronological order in which the tumors appear. Thus, a tumor with few alterations can be occult for years following removal of a more deranged derivative. Extensive genetic damage is seen to accumulate during the evolution of the tumors. To explain the type and extent of genetic damage in combination with the low stage and grade of these tumors, we hypothesize that in bladder cancer pathogenesis an increased rate of mitotic recombination is acquired early in the tumorigenic process.
- Published
- 2000
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