Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer.
Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.|Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Irina V
IV
Kovtun
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Stephen J
SJ
Murphy
Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Sarah H
SH
Johnson
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.|Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
John C
JC
Cheville
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.|Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
George
G
Vasmatzis
D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D043283:Chromosome Fragile Sites; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG
D014408:Biomarkers, Tumor; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
Gleason score; catastrophe; chromothripsis; genomic rearrangements; prostate cancer