Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)29087-29096
Number of pages10
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 2015

Fingerprint

Prostatic Neoplasms
Neoplasms
Neoplasm Grading
Prostatic Intraepithelial Neoplasia
Chromothripsis
Chromosomes
Phenotype

Keywords

  • Catastrophe
  • Chromothripsis
  • Genomic rearrangements
  • Gleason score
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer. / Kovtun, Irina V; Murphy, Stephen J.; Johnson, Sarah H.; Cheville, John C.; Vasmatzis, George.

In: Oncotarget, Vol. 6, No. 30, 2015, p. 29087-29096.

Research output: Contribution to journalArticle

Kovtun, Irina V ; Murphy, Stephen J. ; Johnson, Sarah H. ; Cheville, John C. ; Vasmatzis, George. / Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer. In: Oncotarget. 2015 ; Vol. 6, No. 30. pp. 29087-29096.
@article{fb9a607eac164b269ff0bbb39f82e695,
title = "Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer",
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.",
keywords = "Catastrophe, Chromothripsis, Genomic rearrangements, Gleason score, Prostate cancer",
author = "Kovtun, {Irina V} and Murphy, {Stephen J.} and Johnson, {Sarah H.} and Cheville, {John C.} and George Vasmatzis",
year = "2015",
doi = "10.18632/oncotarget.4900",
language = "English (US)",
volume = "6",
pages = "29087--29096",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "30",

}

TY - JOUR

T1 - Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer

AU - Kovtun, Irina V

AU - Murphy, Stephen J.

AU - Johnson, Sarah H.

AU - Cheville, John C.

AU - Vasmatzis, George

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Catastrophe

KW - Chromothripsis

KW - Genomic rearrangements

KW - Gleason score

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=84945156303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945156303&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.4900

DO - 10.18632/oncotarget.4900

M3 - Article

C2 - 26337081

AN - SCOPUS:84945156303

VL - 6

SP - 29087

EP - 29096

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 30

ER -