CaRLO — Cancer Research Library Online

1

Unknown

Molecular highly efficient research with prostate cancer

Schlomm,T. ; Sueltmann,H. ; Poustka,A. ; [et al.]

Urologe 46 (9), 1097-1100

add to mindlist on the mindlist

Keywords: CANCER ; tumor ; Germany ; PROSTATE ; LUNG-CANCER ; AMPLIFICATION ; microarrays ; prostate cancer ; PROSTATE-CANCER ; EFFICIENT ; MUTATIONS ; OVEREXPRESSION ; molecular ; HER2 ; GEFITINIB

Type of Publication: Journal article published

PubMed ID: 17628772

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=5103

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

2

Unknown

Identification and validation of clinically relevant molecular alterations in prostate cancer

Schlomm,T. ; Sueltmann,H. ; Koellermann,J.

Urologe 47 (9), 1193-1198

add to mindlist on the mindlist

Details

Keywords: CANCER ; Germany ; human ; PROSTATE ; THERAPY ; DIAGNOSIS ; GENE ; GENES ; PROTEIN ; PROTEINS ; validation ; MARKER ; BIOMARKERS ; TARGET ; IDENTIFICATION ; PROGRESSION ; prostate cancer ; PROSTATE-CANCER ; FUSION ; MARKERS ; PREDICTION ; TARGETS ; HUMAN GENES ; molecular biology ; molecular ; THERAPIES ; TISSUE MICROARRAYS ; LEVEL ; biomarker ; analysis ; HIGH-THROUGHPUT ; technique ; CANCERS ; CHALLENGES ; TARGETED THERAPY ; CLINICAL-PRACTICE ; gene protein

Abstract: Significant cellular alterations required for the development and progression of cancers are detectable at the molecular level and represent potential targets for gene-specific therapies. Modern chip techniques allow the parallel analysis of virtually all known human genes and proteins in a single experiment. Using modern high-throughput techniques, numerous potential new biomarkers for the diagnosis and prediction of prostate cancer have been identified. However, so far none of these markers has improved clinical practice. One of the most important challenges in the coming years is the extensive clinical validation of molecular data using clinically relevant end points. For this venture the pivotal prerequisite is the availability of large, comprehensively annotated and standardized high-quality bioresources

Type of Publication: Journal article published

PubMed ID: 18712514

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=6960

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

3

Unknown

Identification and validation of clinically relevant molecular alterations in prostate cancer

Schlomm,T. ; Sueltmann,H. ; Kollermann,J.

Pathologe 30 (2), 111-116

add to mindlist on the mindlist

Details

Keywords: CANCER ; EXPRESSION ; Germany ; human ; PROSTATE ; THERAPY ; DIAGNOSIS ; GENE ; GENES ; PROTEIN ; PROTEINS ; validation ; BIOMARKERS ; IDENTIFICATION ; PROGRESSION ; prostate cancer ; PROSTATE-CANCER ; FUSION ; TARGETS ; SINGLE ; molecular biology ; THERAPIES ; TISSUE MICROARRAYS ; development ; HIGH-THROUGHPUT ; USA ; CANCERS ; TARGETED THERAPY ; ANNEXIN A3

Abstract: Significant cellular alterations required for the development and progression of cancers are detectable at the molecular level and represent potential targets for gene-specific therapies. Modern chip techniques allow the parallel analysis of virtually all known human genes and proteins in a single experiment. Using modern high-throughput techniques, numerous potential new biomarkers for the diagnosis and prediction of prostate cancer have been identified. However, so far none of these markers has improved clinical practice. One of the most important challenges in the coming years is the extensive clinical validation of molecular data using clinically relevant end points. For this venture the pivotal prerequisite is the availability of large, comprehensively annotated and standardized high-quality bioresources

Type of Publication: Journal article published

PubMed ID: 19139898

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=8259

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

4

Unknown

Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform

Ummanni R ; Mundt F ; Pospisil H ; [et al.]

PLoS ONE 6 (2), e16833-

add to mindlist on the mindlist

Details

Keywords: EXPRESSION ; prognosis ; BIOMARKERS ; PROGRESSION ; statistics ; PROTEOMIC ANALYSIS ; ANDROGEN RECEPTOR ; ARGINASE-II ; PEROXIREDOXINS ; PRINCIPLE

Abstract: Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.

DOI: 10.1371/journal.pone.0016833

Type of Publication: Journal article published

PubMed ID: 21347291

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=26874

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

5

Unknown

Extraction and processing of high quality RNA from impalpable and macroscopically invisible prostate cancer for microarray gene expression analysis

Schlomm,T. ; Luebke,A.M. ; Sueltmann,H. ; [et al.]

International Journal of Oncology 27 (3), 713-720

add to mindlist on the mindlist

Details

Keywords: CANCER ; EXPRESSION ; IN-VITRO ; tumor ; carcinoma ; COMBINATION ; Germany ; PROSTATE ; VITRO ; POPULATION ; CDNA ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; microarray ; PROTEIN ; RNA ; transcription ; TISSUE ; MECHANISM ; BIOMARKERS ; mechanisms ; DOWN-REGULATION ; PROGRESSION ; gene expression ; microarrays ; prostate cancer ; PROSTATE-CANCER ; LOCALIZATION ; CARCINOMAS ; CDNA MICROARRAYS ; microdissection ; prostate carcinoma ; QUANTITIES ; MANAGEMENT ; CDNA MICROARRAY ; HETEROGENEITY ; molecular ; RADICAL PROSTATECTOMY ; EXTRACTION ; PROTOCOL ; MOLECULAR-MECHANISMS ; biomarker ; RECOVERY ; RNAS ; PRESERVATION ; HIGH-GRADE ; NEEDLE BIOPSIES ; ALTERNATE READING FRAME ; COA RACEMASE P504S ; ISCHEMIA TIME ; laser microdissection ; tissue banking

Abstract: Molecular analyses of early-stage prostate cancers are necessary to assess their potential clinical significance based on established and/or novel biomarkers for tailored clinical management. A prerequisite for the application of RNA-based analyses of such, mostly macroscopically-undetectable, small prostate carcinomas is the recovery and preservation of sufficient RNA quantities and quality. Furthermore, in prostate cancer, heterogeneity is a common phenomenon that includes a juxtaposition of different tissue compositions and variable histological grades within the same tumor focus. To better understand the molecular mechanisms of prostate cancer, it is essential to correlate molecular data with a specific cell type. Here, we present a tissue collecting protocol which is aligned with the preoperative evaluation of tumor localization. In combination with the technique of laser microdissection and pressure catapulting, we are able to preserve RNA of high quality from homogeneous cell populations of macroscopically-undetectable small prostate carcinomas. To obtain the necessary RNA quantities for whole genome cDNA microarrays, the isolated total RNAs were amplified by T7-based RNA-polymerase in vitro transcription. The microarray analyses (Human Unigene Set RZPD3.1) resulted in 216 differentially expressed genes (191 down-regulated, 25 Up-regulated). Among these were several known prostate cancer relevant genes, such as AMACR, TARP, LIM, GPR160 (all up-regulated), CAVI, NTNI, MTIX; CLU, TRIM29, SPARCLI and HSPB8 (,all down-regulated)

Type of Publication: Journal article published

PubMed ID: 16077921

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=2649

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

6

Unknown

ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy

Minner S ; Enodien M ; Sirma H ; [et al.]

Clinical Cancer Research 17 (18), 5878-5888

add to mindlist on the mindlist

Details

Keywords: EXPRESSION ; TUMOR-CELLS ; PROGRESSION ; IN-SITU HYBRIDIZATION ; OVEREXPRESSION ; POOR-PROGNOSIS ; PTEN ; ANDROGEN RECEPTOR ; ETS FAMILY ; TMPRSS2-ERG GENE FUSION

Abstract: PURPOSE: About 50% of prostate cancers have TMPRSS2-ERG fusions with concurrent ERG overexpression. The aim of this study was to determine whether clinical differences exist between ERG-positive and ERG-negative cancers in surgically treated patients not exposed to antihormonal therapy. A secondary aim was to search for differences between these tumor classes. EXPERIMENTAL DESIGN: A tissue microarray containing samples from more than 2,800 prostate cancers with clinical data was analyzed for ERG alterations by immunohistochemistry and FISH. Results were compared with tumor phenotype, biochemical recurrence, and molecular features considered important for prostate cancer. The effect of ERG on androgen receptor (AR)-dependent transcription was analyzed in cell lines. RESULTS: ERG expression was found in 52.4% of 2,805 cancers with a 95% concordance between ERG expression and ERG gene rearrangement detected by FISH. ERG expression was unrelated to clinical outcome and tumor phenotype. Differences in AMACR, Annexin A3, Bcl2, CD10, ALCAM, chromogranin A, epidermal growth factor receptor, HER2, mTOR, p53, and synaptophysin status were significant but minimal in absolute numbers. The most striking difference was found for AR expression, which was markedly higher in ERG-positive cancers. In vitro studies showed ERG-dependent impairment of AR-mediated transcriptional activity. CONCLUSIONS: The striking similarities between these two types of prostate cancers rules out a major impact of ERG on tumor aggressiveness in early, not hormonally treated cancer. The marked difference in AR levels between ERG-positive and -negative cancers supports a systematic difference in potential response to hormonal therapy as previously observed in clinical trials.

DOI: 10.1158/1078-0432.CCR-11-1251

Type of Publication: Journal article published

PubMed ID: 21791629

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=28382

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

7

Unknown

Genomic Deletion of PTEN Is Associated with Tumor Progression and Early PSA Recurrence in ERG Fusion-Positive and Fusion-Negative Prostate Cancer

Krohn A ; Diedler T ; Burkhardt L ; [et al.]

American Journal of Pathology 181 (2), 401-412

add to mindlist on the mindlist

Details

Keywords: EXPRESSION ; GENE ; PROTEIN ; HIGH-RISK ; POOR-PROGNOSIS ; AKT ; IMMUNOHISTOCHEMICAL DETECTION ; PTEN/MMAC1 ; SUPPRESSOR ; FISH ANALYSIS

Abstract: The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naive and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P 〈 0.0001), high Gleason grade (P 〈 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P 〈 0.0001), presence of ERG gene fusion (P 〈 0.0001), and nuclear p53 accumulation (P 〈 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P 〈 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers.

DOI: 10.1016/j.ajpath.2012.04.026

Type of Publication: Journal article published

PubMed ID: 22705054

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=33001

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

8

Unknown

Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation

Boerno ST ; Fischer A ; Kerick M ; [et al.]

Cancer Discovery 2 (11), 1024-1035

add to mindlist on the mindlist

Details

Keywords: CELLS ; EXPRESSION ; GROWTH ; DIFFERENTIATION ; PROGRESSION ; REPRESSION ; NASOPHARYNGEAL CARCINOMA ; GROUP PROTEIN EZH2 ; POLYCOMB ; GENE FUSIONS

Abstract: Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the first high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing. Comparative analyses identified more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show significant differences based on the TMPRSS2-ERG rearrangement status. We propose the hypermethylation of miR-26a as an alternative pathway of ERG rearrangement-independent EZH2 activation. The observed increase in differential methylation events in fusion-negative tumors can explain the tumorigenic process in the absence of genomic rearrangements. SIGNIFICANCE: In contrast to TMPRSS2-ERG -rearranged tumors, the pathomechanism for gene fusion-negative tumors is completely unclear. Using a sequencing-based approach, our work uncovers significant global epigenetic alterations in TMPRSS2-ERG gene fusion-negative tumors and provides a mechanistic explanation for the tumor formation process.

DOI: 10.1158/2159-8290.CD-12-0041

Type of Publication: Journal article published

PubMed ID: 22930729

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=37380

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

9

Unknown

Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer

Weischenfeldt, J.*, Simon, R.* ; Feuerbach, L.* ; Schlangen, K.* ; [et al.]

Cancer Cell 23 (2), 159-170

add to mindlist on the mindlist

Details

Keywords: RECEPTOR ; MECHANISM ; DELETION ; PROGRESSION ; MEN ; MYELOID-LEUKEMIA ; REARRANGEMENTS ; GENE FUSIONS ; SEQUENCING DATA ; PSA RECURRENCE

Abstract: Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of 〉 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

DOI: 10.1016/j.ccr.2013.01.002

Type of Publication: Journal article published

PubMed ID: 23410972

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=35172

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION

10

Unknown

Genomic deletion of MAP3K7 at 6q12-22 is associated with early PSA recurrence in prostate cancer and absence of TMPRSS2:ERG fusions

Kluth M ; Hesse J ; Heinl A ; [et al.]

Modern Pathology 26 (7), 975-983

add to mindlist on the mindlist

Details

Keywords: PATHWAYS ; BREAST-CANCER ; PROGRESSION ; SIGNAL-TRANSDUCTION ; TUMOR-SUPPRESSOR GENE ; PTEN ; MAPK ; TUMORIGENESIS ; BETA-ACTIVATED KINASE-1 ; TAK1

Abstract: 6q12-22 is the second most commonly deleted genomic region in prostate cancer. Mapping studies have described a minimally deleted area at 6q15, containing MAP3K7/TAK1, which was recently shown to have tumor suppressive properties. To determine prevalence and clinical significance of MAP3K7 alterations in prostate cancer, a tissue microarray containing 4699 prostate cancer samples was analyzed by fluorescence in situ hybridization. Heterozygous MAP3K7 deletions were found in 18.48% of 2289 interpretable prostate cancers. MAP3K7 deletions were significantly associated with advanced tumor stage (P〈0.0001), high Gleason grade (P〈0.0001), lymph node metastasis (P〈0.0108) and early biochemical recurrence (P〈0.0001). MAP3K7 alterations were typically limited to the loss of one allele as homozygous deletions were virtually absent and sequencing analyses revealed no evidence for MAP3K7 mutations in 15 deleted and in 14 non-deleted cancers. There was a striking inverse association of MAP3K7 deletions and TMPRSS2:ERG fusion status with 26.7% 6q deletions in 1125 ERG-negative and 11.1% 6q deletions in 1198 ERG-positive cancers (P〈0.0001). However, the strong prognostic role of 6q deletions was retained in both ERG-positive and ERG-negative cancers (P〈0.0001 each). In summary, our study identifies MAP3K7 deletion as a prominent feature in ERG-negative prostate cancer with strong association to tumor aggressiveness. MAP3K7 alterations are typically limited to one allele of the gene. Together with the demonstrated tumor suppressive function in cell line experiments and lacking evidence for inactivation through hypermethylation, these results indicate MAP3K7 as a gene for which haploinsufficency is substantially tumorigenic.

DOI: 10.1038/modpathol.2012.236

Type of Publication: Journal article published

PubMed ID: 23370768

Deep Link: http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=41065

Permalink

Signatur	Availability

Others were also interested in ...

DKFZ PUBLICATION