Oncotarget

Research Papers:

Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer

Irina V. Kovtun _, Stephen J. Murphy, Sarah H. Johnson, John C. Cheville and George Vasmatzis

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Oncotarget. 2015; 6:29087-29096. https://doi.org/10.18632/oncotarget.4900

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Abstract

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

Correspondence to:

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

ABSTRACT

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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