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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.

SUBMITTER: Kovtun IV

PROVIDER: S-EPMC4745713 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer.

Kovtun Irina V IV Murphy Stephen J SJ Johnson Sarah H SH Cheville John C JC Vasmatzis George G

Oncotarget 20151001 30

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 prosta ...[more]

PMID: 26337081

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Project description:Objectives: To develop and validate a predictive model for discriminating clinically significant prostate cancer (csPCa) from clinically insignificant prostate cancer (ciPCa). Methods: This retrospective study was performed with 159 consecutively enrolled pathologically confirmed PCa patients from two medical centers. The dataset was allocated to a training group (n = 54) and an internal validation group (n = 22) from one center along with an external independent validation group (n = 83) from another center. A total of 1,188 radiomic features were extracted from T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images derived from DWI for each patient. Multivariable logistic regression analysis was performed to develop the model, incorporating the radiomic signature, ADC value, and independent clinical risk factors. This was presented using a radiomic nomogram. The receiver operating characteristic (ROC) curve was utilized to assess the predictive efficacy of the radiomic nomogram in both the training and validation groups. The decision curve analysis was used to evaluate which model achieved the most net benefit. Results: The radiomic signature, which was made up of 10 selected features, was significantly associated with csPCa (P < 0.001 for both training and internal validation groups). The area under the curve (AUC) values of discriminating csPCa for the radiomics signature were 0.95 (training group), 0.86 (internal validation group), and 0.81 (external validation group). Multivariate logistic analysis identified the radiomic signature and ADC value as independent parameters of predicting csPCa. Then, the combination nomogram incorporating the radiomic signature and ADC value demonstrated a favorable classification capability with the AUC of 0.95 (training group), 0.93 (internal validation group), and 0.84 (external validation group). Appreciable clinical utility of this model was illustrated using the decision curve analysis for the nomogram. Conclusions: The nomogram, incorporating radiomic signature and ADC value, provided an individualized, potential approach for discriminating csPCa from ciPCa.

Dataset Information

Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer.

Publications

Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer.

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