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Large Chromosomal Rearrangements Yield Biomarkers to Distinguish Low-Risk From Intermediate- and High-Risk Prostate Cancer
- Source :
- Mayo Clinic Proceedings. 94:27-36
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Objective To test the hypothesis that chromosomal rearrangements (CRs) can distinguish low risk of progression (LRP) from intermediate and high risk of progression (IHRP) to prostate cancer (PCa) and if these CRs have the potential to identify men with LRP on needle biopsy that harbor IHRP PCa in the prostate gland. Patients and Methods Mate pair sequencing of amplified DNA from pure populations of Gleason patterns in 154 frozen specimens from 126 patients obtained between August 14, 2001, and July 15, 2011, was used to detect CRs including abnormal junctions and copy number variations. Potential CR biomarkers with higher incidence in IHRP than in LRP to cancer and having significance in PCa biology were identified. Independent validation was performed by fluorescence in situ hybridization in 152 specimens from 124 patients obtained between February 12, 2002, and July 12, 2008. Results The number of abnormal junctions did not distinguish LRP from IHRP. Loci corresponding to genes implicated in PCa were more frequently altered in IHRP. Integrated analysis of copy number variations and microarray data yielded 6 potential markers that were more frequently detected in Gleason pattern 3 of a Gleason score 7 of PCa than in Gleason pattern 3 of a Gleason score 6 PCa. Five of those were cross-validated in an independent sample set with statistically significant areas under the receiver operating characteristic curves (AUCs) (P≤.01). Probes detecting deletions in PTEN and CHD1 had AUCs of 0.87 (95% CI, 0.77-0.97) and 0.73 (95% CI, 0.60-0.86), respectively, and probes detecting gains in ASAP1, MYC, and HDAC9 had AUCs of 0.71 (95% CI, 0.59-0.84), 0.82 (95% CI, 0.71-0.93), and 0.77 (95% CI, 0.66-0.89), respectively (for expansion of gene symbols, use search tool at www.genenames.org). Conclusion Copy number variations in regions encompassing important PCa genes were predictive of cancer significance and have the potential to identify men with LRP PCa by needle biopsy who have IHRP PCa in their prostate gland.
- Subjects :
- Male
Oncology
medicine.medical_specialty
DNA Copy Number Variations
Chromosomal rearrangement
urologic and male genital diseases
Gleason Score 6
Prostate cancer
Risk Factors
Internal medicine
Biomarkers, Tumor
Humans
Medicine
PTEN
Copy-number variation
In Situ Hybridization, Fluorescence
Aged
Neoplasm Staging
Retrospective Studies
Receiver operating characteristic
medicine.diagnostic_test
biology
business.industry
Biopsy, Needle
Prostate
Prostatic Neoplasms
Cancer
DNA, Neoplasm
General Medicine
Middle Aged
medicine.disease
ROC Curve
Disease Progression
biology.protein
business
Follow-Up Studies
Fluorescence in situ hybridization
Subjects
Details
- ISSN :
- 00256196
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Mayo Clinic Proceedings
- Accession number :
- edsair.doi.dedup.....09314a19d20685253cbbd5176d78103a