DNA copy number alteration analysis and gene expression profiles comparing radioresistant to radiosensitive prostate cancer cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134500 | GEO | 2019/10/11
REPOSITORIES: GEO
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Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. aCGH profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured and compared to normal DNA.
2019-10-11 | GSE134498 | GEO
Project description:DNA copy number alteration analysis and gene expression profiles comparing radioresistant to radiosensitive prostate cancer cell lines
| PRJNA555334 | ENA
Project description:DNA copy number alteration analysis of radioresistant and radiosensitive prostate cancer cell lines
| PRJNA555346 | ENA
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. Gene expression profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured.
2019-10-11 | GSE134499 | GEO
Project description: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 whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.
| S-EPMC4121784 | biostudies-other
Project description:BackgroundDuring cancer progression, malignant cells accumulate somatic mutations that can lead to genetic aberrations. In particular, evolutionary events akin to segmental duplications or deletions can alter the copy-number profile (CNP) of a set of genes in a genome. Our aim is to compute the evolutionary distance between two cells for which only CNPs are known. This asks for the minimum number of segmental amplifications and deletions to turn one CNP into another. This was recently formalized into a model where each event is assumed to alter a copy-number by 1 or -1, even though these events can affect large portions of a chromosome.ResultsWe propose a general cost framework where an event can modify the copy-number of a gene by larger amounts. We show that any cost scheme that allows segmental deletions of arbitrary length makes computing the distance strongly NP-hard. We then devise a factor 2 approximation algorithm for the problem when copy-numbers are non-zero and provide an implementation called cnp2cnp. We evaluate our approach experimentally by reconstructing simulated cancer phylogenies from the pairwise distances inferred by cnp2cnp and compare it against two other alternatives, namely the MEDICC distance and the Euclidean distance.ConclusionsThe experimental results show that our distance yields more accurate phylogenies on average than these alternatives if the given CNPs are error-free, but that the MEDICC distance is slightly more robust against error in the data. In all cases, our experiments show that either our approach or the MEDICC approach should preferred over the Euclidean distance.
| S-EPMC7160889 | biostudies-literature
Project description:BackgroundDistinguishing between true indolent and potentially life-threatening prostate cancer is challenging in tumours displaying clinicopathologic features associated with low or intermediate risk of relapse. Several somatic DNA copy number alterations (CNAs) have been identified as potential prognostic biomarkers, but the standard cytogenetic method to assess them has a limited multiplexing capability.MethodsMultiplex ligation-dependent probe amplification (MLPA) targeting 14 genes was optimised to survey 448 tumours of patients with low or intermediate risk (Grade Group 1-3, Gleason score ≤7) who underwent radical prostatectomy. A 6-gene CNA classifier was developed using random survival forest and Cox proportional hazard modelling to predict biochemical recurrence.ResultsThe classifier score was significantly associated with biochemical recurrence after adjusting for standard clinicopathologic variables and the known prognostic index CAPRA-S score with a hazard ratio of 2.17 and 1.80, respectively (n = 406, P < 0.01). The prognostic value of this classifier was externally validated in published CNA data from three radical prostatectomy cohorts and one radiation therapy pre-treatment biopsy cohort.ConclusionThe 6-gene CNA classifier generated by a single MLPA assay compatible with the small quantities of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens has the potential to improve the clinical management of patients with low or intermediate risk disease.
| S-EPMC10241891 | biostudies-literature
Project description:Comparative analysis of gene expression profiles comparing radioresistant to radiosensitive prostate cancer cell lines
| PRJNA555347 | ENA
Project description:SummarySelecting the optimal cancer cell line for an experiment can be challenging given the diversity of lines available. Here, we present CNpare, which identifies similar cell line models based on genome-wide DNA copy number.AvailabilityCNpare is available as an R package at https://github.com/macintyrelab/CNpare. All analysis performed in the manuscript can be reproduced via the code found at https://github.com/macintyrelab/CNpare_analyses.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9272807 | biostudies-literature
Project description:BACKGROUND:Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles. RESULTS:Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167). CONCLUSION:Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis.
| S-EPMC4289277 | biostudies-literature