Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.

Antje Krohn; Tobias Diedler; Lia Burkhardt; Pascale S Mayer; De Silva Colin; Marie Meyer-Kornblum; Darja Kötschau; Pierre Tennstedt; Joseph Huang; Clarissa Gerhäuser; Malte Mader; Stefan Kurtz; Hüseyin Sirma; Fred Saad; Thomas Steuber; Markus Graefen; Christoph Plass; Guido Sauter; Ronald Simon; Sarah Jane Pauline Minner; Thorsten Schlomm

Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.

Standard

Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. / Krohn, Antje; Diedler, Tobias; Burkhardt, Lia; Mayer, Pascale S; Colin, De Silva; Meyer-Kornblum, Marie; Kötschau, Darja; Tennstedt, Pierre; Huang, Joseph; Gerhäuser, Clarissa; Mader, Malte; Kurtz, Stefan; Sirma, Hüseyin; Saad, Fred; Steuber, Thomas; Graefen, Markus; Plass, Christoph; Sauter, Guido ; Simon, Ronald ; Minner, Sarah Jane Pauline; Schlomm, Thorsten.

In: AM J PATHOL, Vol. 181, No. 2, 2, 2012, p. 401-412.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Krohn, A, Diedler, T, Burkhardt, L, Mayer, PS, Colin, DS, Meyer-Kornblum, M, Kötschau, D, Tennstedt, P, Huang, J, Gerhäuser, C, Mader, M, Kurtz, S, Sirma, H, Saad, F, Steuber, T, Graefen, M, Plass, C, Sauter, G , Simon, R , Minner, SJP & Schlomm, T 2012, 'Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.', AM J PATHOL, vol. 181, no. 2, 2, pp. 401-412. <http://www.ncbi.nlm.nih.gov/pubmed/22705054?dopt=Citation>

APA

Krohn, A., Diedler, T., Burkhardt, L., Mayer, P. S., Colin, D. S., Meyer-Kornblum, M., Kötschau, D., Tennstedt, P., Huang, J., Gerhäuser, C., Mader, M., Kurtz, S., Sirma, H., Saad, F., Steuber, T., Graefen, M., Plass, C., Sauter, G., Simon, R., ... Schlomm, T. (2012). Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. AM J PATHOL, 181(2), 401-412. [2]. http://www.ncbi.nlm.nih.gov/pubmed/22705054?dopt=Citation

Vancouver

Krohn A, Diedler T, Burkhardt L, Mayer PS, Colin DS, Meyer-Kornblum M et al. Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. AM J PATHOL. 2012;181(2):401-412. 2.

Bibtex

@article{dd96ff2270b34e6bbd36cbd9768809b2,

title = "Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.",

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-na{\"i}ve 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.",

keywords = "Humans, Male, Aged, Middle Aged, Multivariate Analysis, Immunohistochemistry, Disease Progression, Proportional Hazards Models, DNA Mutational Analysis, Phenotype, Recurrence, *Gene Deletion, Tumor Suppressor Protein p53/metabolism, Tumor Markers, Biological/metabolism, Polymorphism, Single Nucleotide/genetics, Prostate-Specific Antigen/*metabolism, Promoter Regions, Genetic/genetics, Trans-Activators/*metabolism, DNA Methylation/genetics, Epigenesis, Genetic, Chromosomes, Human, Pair 10/genetics, Genome, Human/genetics, Oncogene Proteins, Fusion/*metabolism, PTEN Phosphohydrolase/*genetics/metabolism, Prostatic Neoplasms/*enzymology/*pathology, Humans, Male, Aged, Middle Aged, Multivariate Analysis, Immunohistochemistry, Disease Progression, Proportional Hazards Models, DNA Mutational Analysis, Phenotype, Recurrence, *Gene Deletion, Tumor Suppressor Protein p53/metabolism, Tumor Markers, Biological/metabolism, Polymorphism, Single Nucleotide/genetics, Prostate-Specific Antigen/*metabolism, Promoter Regions, Genetic/genetics, Trans-Activators/*metabolism, DNA Methylation/genetics, Epigenesis, Genetic, Chromosomes, Human, Pair 10/genetics, Genome, Human/genetics, Oncogene Proteins, Fusion/*metabolism, PTEN Phosphohydrolase/*genetics/metabolism, Prostatic Neoplasms/*enzymology/*pathology",

author = "Antje Krohn and Tobias Diedler and Lia Burkhardt and Mayer, {Pascale S} and Colin, {De Silva} and Marie Meyer-Kornblum and Darja K{\"o}tschau and Pierre Tennstedt and Joseph Huang and Clarissa Gerh{\"a}user and Malte Mader and Stefan Kurtz and H{\"u}seyin Sirma and Fred Saad and Thomas Steuber and Markus Graefen and Christoph Plass and Guido Sauter and Ronald Simon and Minner, {Sarah Jane Pauline} and Thorsten Schlomm",

year = "2012",

language = "English",

volume = "181",

pages = "401--412",

journal = "AM J PATHOL",

issn = "0002-9440",

publisher = "Elsevier Inc.",

number = "2",

}

RIS

TY - JOUR

T1 - Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.

AU - Krohn, Antje

AU - Diedler, Tobias

AU - Burkhardt, Lia

AU - Mayer, Pascale S

AU - Colin, De Silva

AU - Meyer-Kornblum, Marie

AU - Kötschau, Darja

AU - Tennstedt, Pierre

AU - Huang, Joseph

AU - Gerhäuser, Clarissa

AU - Mader, Malte

AU - Kurtz, Stefan

AU - Sirma, Hüseyin

AU - Saad, Fred

AU - Steuber, Thomas

AU - Graefen, Markus

AU - Plass, Christoph

AU - Sauter, Guido

AU - Simon, Ronald

AU - Minner, Sarah Jane Pauline

AU - Schlomm, Thorsten

PY - 2012

Y1 - 2012

N2 - 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-naïve 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.

AB - 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-naïve 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.

KW - Humans

KW - Male

KW - Aged

KW - Middle Aged

KW - Multivariate Analysis

KW - Immunohistochemistry

KW - Disease Progression

KW - Proportional Hazards Models

KW - DNA Mutational Analysis

KW - Phenotype

KW - Recurrence

KW - Gene Deletion

KW - Tumor Suppressor Protein p53/metabolism

KW - Tumor Markers, Biological/metabolism

KW - Polymorphism, Single Nucleotide/genetics

KW - Prostate-Specific Antigen/metabolism

KW - Promoter Regions, Genetic/genetics

KW - Trans-Activators/metabolism

KW - DNA Methylation/genetics

KW - Epigenesis, Genetic

KW - Chromosomes, Human, Pair 10/genetics

KW - Genome, Human/genetics

KW - Oncogene Proteins, Fusion/metabolism

KW - PTEN Phosphohydrolase/genetics/metabolism

KW - Prostatic Neoplasms/enzymology/pathology