Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer
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Irina V. Kovtun1,4, Stephen J. Murphy2,4, Sarah H. Johnson4, John C. Cheville3,4, George Vasmatzis2,4
1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA
2Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
3Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
4Department of Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA
Irina V. Kovtun, e-mail: Kovtun.Irina@mayo.edu
George Vasmatzis, e-mail: Vasmatzis.George@mayo.edu
Keywords: chromothripsis, catastrophe, genomic rearrangements, prostate cancer, gleason score
Received: June 04, 2015 Accepted: August 11, 2015 Published: August 21, 2015
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.
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