Transcriptome-Wide Detection of Differentially Expressed Coding and Non-Coding Transcripts and Their Clinical Significance in Prostate Cancer

Erho, Nicholas; Buerki, Christine; Triche, Timothy J.; Davicioni, Elai; Vergara, Ismael A.

doi:10.1155/2012/541353

Cited by 14 publications

(12 citation statements)

References 34 publications

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“…We have collected the clinically annotated cohorts presented here to help address these challenges. The initial cohort has been used extensively by others for prognostic discovery and validation (7,8,27) and is updated here by providing a definitive clinical endpoint, metastasis, in significant numbers. The additional independent contemporary cohort now provides a resource for validation of CNA as a prognostic factor and other associations.…”

Section: Discussionmentioning

confidence: 99%

Copy number alteration burden predicts prostate cancer relapse

Hieronymus¹,

Schultz

Gopalan³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

310

260

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Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input wholegenome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.genomics | prognosis | oncology P rostate cancer is the second leading cause of cancer death and the most common malignancy in men. Given the slow growth rate and low metastatic potential of many primary prostate cancers (1), it is critical to identify those men who can be managed conservatively through active surveillance versus those who need aggressive therapy at time of first diagnosis (2, 3). Today, these treatment decisions are primarily made on the basis of tumor stage, prostate-specific antigen (PSA) level, and the histopathological measure of tumor cell differentiation, the Gleason score. These three factors, together with additional pathological variables assessed in the prostatectomy sample, such as lymph node involvement, are often used to estimate risk of relapse with accuracies in the 70-80% range (3). Postoperative nomograms that incorporate these variables have been developed using large cohorts of typically >1,000 patients and consistently show greater accuracy than preoperative nomograms, where pathological variables are limited to those than can be gleaned from biopsies (4). With increasing interest in active surveillance, however, it is critical to improve risk prediction in the preoperative setting (5, 6).

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Section: Discussionmentioning

confidence: 99%

Copy number alteration burden predicts prostate cancer relapse

Hieronymus¹,

Schultz

Gopalan³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

310

260

View full text Add to dashboard Cite

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“…A number of prostate tumor biomarkers have been identified that may define heterogeneity of CaP etiology 59, 60 , have clinical implications for surveillance and treatment (reviewed in 61 ), or correlate with aggressive phenotypes 62-69 . Among these are the TMPRSS2:ERG gene fusion/translocation 70 , Ki-67 expression 64 , biomarkers involved in androgen metabolism 65, 71 and genomic classifiers that use a whole-transcriptome microarray assays to analyze gene activity in prostate cancer specimens 72 . In general, the majority of the studies of these biomarkers has been in European- or Asian-descent populations, are there are limited data that evaluate whether these markers have similar distributions or confer similar effects on outcomes in African descent populations.…”

Section: Tumor Biomarkersmentioning

confidence: 99%

Prostate Cancer Genetics: Variation by Race, Ethnicity, and Geography

Rebbeck

2017

Seminars in Radiation Oncology

253

189

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Prostate cancer rates vary substantially by race, ethnicity, and geography. These disparities can be explained by variation in access to screening and treatment, variation in exposure to prostate cancer risk factors, and variation in the underlying biology of prostate carcinogenesis (including genomic propensity of some groups to develop biologically aggressive disease). It is clear that access to screening and treatment are critical influencers of prostate cancer rates, yet even among geographically diverse populations with similar access to care (e.g., low and medium income countries), African descent men have higher prostate cancer rates and poorer prognosis. To date, the proportion of prostate cancer that can be explained by environmental exposures is small, and the impact of these factors across different racial, ethnic, or geographical populations is poorly understood. In contrast, prostate cancer has one of the highest heritabilities of all major cancers. Numerous genetic susceptibility markers have been identified from family-based studies, candidate gene association studies, and genome-wide association studies. Some prostate cancer loci, including the risk loci found at chromosome 8q24, have consistent effects in all groups studied to date. However, replication of many susceptibility loci across race, ethnicity, and geography remains limited, and additional studies in certain populations (particularly in men of African descent) are needed to better understand the underlying genetic basis of prostate cancer.

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“…Erho and colleagues found that EEF1DP3 is differentially expressed between normal prostate tissues and primary and metastatic prostate cancer samples (Erho et al, 2012) EEF1DP3/BLVRB (https://fusionhub.persistent.co.in/home.html). Hybrid/Mutated gene The t(13;19)(q13;q13) EEF1DP3/BLVRB was found in sarcoma.…”

Section: Prostate Cancermentioning

confidence: 99%