Molecular evolution of multiple recurrent cancers of the bladder.
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.
van Tilborg
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AA
Department of Pathology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
de Vries
A
A
de Bont
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M
Groenfeld
L E
LE
van der Kwast
T H
TH
Zwarthoff
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EC
D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3