Search

Your search keyword '"Granberg K"' showing total 3 results
Start Over Author "Granberg K" Topic prostatic neoplasms
3 results on '"Granberg K"'

1. Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse.

Author

Taavitsainen S, Engedal N, Cao S, Handle F, Erickson A, Prekovic S, Wetterskog D, Tolonen T, Vuorinen EM, Kiviaho A, Nätkin R, Häkkinen T, Devlies W, Henttinen S, Kaarijärvi R, Lahnalampi M, Kaljunen H, Nowakowska K, Syvälä H, Bläuer M, Cremaschi P, Claessens F, Visakorpi T, Tammela TLJ, Murtola T, Granberg KJ, Lamb AD, Ketola K, Mills IG, Attard G, Wang W, Nykter M, and Urbanucci A

Subjects
Antineoplastic Agents therapeutic use, Benzamides therapeutic use, Cell Line, Tumor, Chromatin metabolism, DNA, Neoplasm metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Proteins metabolism, Nitriles therapeutic use, Phenylthiohydantoin therapeutic use, Prostate metabolism, Prostate pathology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms mortality, Prostatic Neoplasms pathology, Sequence Analysis, RNA methods, Single-Cell Analysis methods, Survival Analysis, Exome Sequencing, Chromatin chemistry, DNA, Neoplasm genetics, Drug Resistance, Neoplasm genetics, Neoplasm Proteins genetics, Prostatic Neoplasms genetics, Transcriptome
Abstract

Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making., (© 2021. The Author(s).)

Published
2021
Full Text
View/download PDF

2. Recurrent SKIL-activating rearrangements in ETS-negative prostate cancer.

Author

Annala M, Kivinummi K, Tuominen J, Karakurt S, Granberg K, Latonen L, Ylipää A, Sjöblom L, Ruusuvuori P, Saramäki O, Kaukoniemi KM, Yli-Harja O, Vessella RL, Tammela TL, Zhang W, Visakorpi T, and Nykter M

Subjects
Animals, Cell Line, Tumor, Cohort Studies, Gene Knockdown Techniques, Gene Rearrangement, Heterografts, Humans, Intracellular Signaling Peptides and Proteins biosynthesis, Intracellular Signaling Peptides and Proteins metabolism, Male, Mice, Middle Aged, Prostatic Neoplasms metabolism, Proto-Oncogene Proteins biosynthesis, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-ets metabolism, Transcriptome, Transfection, Intracellular Signaling Peptides and Proteins genetics, Prostatic Neoplasms classification, Prostatic Neoplasms genetics, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-ets genetics
Abstract

Prostate cancer is the third most common cause of male cancer death in developed countries, and one of the most comprehensively characterized human cancers. Roughly 60% of prostate cancers harbor gene fusions that juxtapose ETS-family transcription factors with androgen regulated promoters. A second subtype, characterized by SPINK1 overexpression, accounts for 15% of prostate cancers. Here we report the discovery of a new prostate cancer subtype characterized by rearrangements juxtaposing the SMAD inhibitor SKIL with androgen regulated promoters, leading to increased SKIL expression. SKIL fusions were found in 6 of 540 (1.1%) prostate cancers and 1 of 27 (3.7%) cell lines and xenografts. 6 of 7 SKIL-positive cancers were negative for ETS overexpression, suggesting mutual exclusivity with ETS fusions. SKIL knockdown led to growth arrest in PC-3 and LNCaP cell line models of prostate cancer, and its overexpression led to increased invasiveness in RWPE-1 cells. The role of SKIL as a prostate cancer oncogene lends support to recent studies on the role of TGF-β signaling as a rate-limiting step in prostate cancer progression. Our findings highlight SKIL as an oncogene and potential therapeutic target in 1-2% of prostate cancers, amounting to an estimated 10,000 cancer diagnoses per year worldwide.

Published
2015
Full Text
View/download PDF

3. Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse

Author

Taavitsainen, S., Engedal, N., Cao, S., Handle, F., Erickson, A., Prekovic, S., Wetterskog, D., Tolonen, T., Vuorinen, E. M., Kiviaho, A., Nätkin, R., Häkkinen, T., Devlies, W., Henttinen, S., Kaarijärvi, R., Lahnalampi, M., Kaljunen, H., Nowakowska, K., Syvälä, H., Bläuer, M., Cremaschi, P., Claessens, F., Visakorpi, T., Tammela, T. L. J., Murtola, T., Granberg, K. J., Lamb, A. D., Ketola, K., Mills, I. G., Attard, G., Wang, W., Nykter, M., Urbanucci, A., Tampere University, BioMediTech, Department of Pathology, Clinical Medicine, TAYS Cancer Centre, and Department of Surgery

Subjects
Male, CHROMATIN, REGULATORY ELEMENTS, Science, 3122 Cancers, Antineoplastic Agents, Article, ANDROGEN-RECEPTOR, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Nitriles, Phenylthiohydantoin, Exome Sequencing, PROGRAM, Humans, TRANSCRIPTION, FAIRE, Prostate cancer, Science & Technology, Sequence Analysis, RNA, Gene Expression Profiling, Prostate, Prostatic Neoplasms, DNA, Neoplasm, Survival Analysis, Chromatin, EVOLUTION, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Multidisciplinary Sciences, HALLMARK, Drug Resistance, Neoplasm, DRIVES, Benzamides, Science & Technology - Other Topics, Data integration, 3111 Biomedicine, Single-Cell Analysis, Transcriptome, RESISTANCE
Abstract

Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identify pre-existing and treatment-persistent cell subpopulations that possess regenerative potential when subjected to treatment. We find distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent cells are able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal as yet unrecognized molecular predictors of treatment response. This suggests that the application of single-cell methods with high analytical resolution in pre-clinical models may powerfully inform clinical decision-making., Identifying the molecular mechanisms of response to systemic therapy in prostate cancer remains crucial. Here, the authors apply single cell-ATAC and RNAseq to models of early treatment response and resistance to enzalutamide and identify chromatin and gene expression patterns that can predict treatment response.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results