The Molecular Biology of Prostate Cancer Group (MBPCG) studies somatic genetic and epigenetic alterations in prostate cancer with emphasis on alterations associated with disease progression. Finding the common genetic alterations is an important step in the development of better diagnostics and therapeutics. Especially, MBPCG is exploring strategies to therapeutically interfere with androgen signaling.
Research interests and expertise
The goal of the research group is to identify recurrent genetic and epigenetic alterations in prostate cancer using modern genomic tools, such as next generation sequencing. Special emphasis is currently placed on non-coding RNAs (ncRNA). In addition, we have a strong interest towards androgen receptor (AR) gene, amplification of which was first described by the group. We study mechanistic consequences of the overexpression of AR using models we have established, as well as clinical samples of castration-resistant disease. We also identify and characterize downstream genes of AR signaling pathway, to screen for candidate drug targets.
We were first to describe AR amplification as a major alteration in progressed prostate cancer (Visakorpi et al. 1995 Nature Genetics), and have since conducted considerable work in understanding molecular biology and downstream effects of AR in prostate cancer. The group has contributed significantly in understanding of genetic, epigenetic and gene expression changes during prostate cancer development and progression. Of candidate drug targets, especially TMPRSS2:ERG fusion gene, as well as our recently discovered microRNA, miR-32, show promise for utility.
We work in brand new laboratories in the ARVO building in the University of Tampere Kauppi campus. We belong to Prostate Cancer Research Center (PCRC) which integrates multidisciplinary research on prostate cancer in the University of Tampere and the Pirkanmaa Hospital District, the second biggest Hospital District in Finland. We have a unique collection of population-based clinical materials and models with complementary expertise from molecular mechanisms to clinical practice. This provides an exceptionally strong basis to find answers to the most important questions in treatment of prostate cancer: the etiology of the disease, identification of clinically relevant disease, personalized cancer therapy and novel treatment modalities to combat the disease.
Gundem G, Van Loo P, Kremeyer B, Alexandrov L, Tubio J, Papaemmanuil E, Brewer D, Kallio H, Högnäs G, Annala M, Goody V, Latimer C, O’Meara S, Dawson K, Isaacs W, Emmert-Buck M, Nykter M, Foster C, Kote-Jarai Z, Easton D, Whitaker H, Neal D, Cooper C, Eeles R, Visakorpi T, Campbell P, McDermott U1, Wedge D1. Bova GS1. The evolutionary history of lethal metastatic prostate cancer. 1shared correspondence.Nature 520:353-357, 2015.
Khanna A, Rane JK, Kivinummi KK, Urbanucci A, Helenius MA, Tolonen TT, Saramäki OR, Latonen L, Manni V, Pimanda JE, Maitland NJ, Westermarck J, Visakorpi T. CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations. Oncotarget 6:19661-70, 2015.
Ylipää A1, Kivinummi K1, Kohvakka A, Annala M, Latonen L, Scaravilli M, Kartasalo K, Leppänen SP, Karakurt S, Seppälä J, Yli-Harja O, Tammela TLJ, Zhang W, Visakorpi T2, Nykter M2. Transcriptome sequencing reveals PCAT5 as a novel ERG-regulated long non-coding RNA in prostate cancer. 1shared first authors; 2shared correspondence, Cancer Res, 75:4026-4031, 2015.
Bova GS1, Kallio H1, Annala M1, Kivinummi K, Högnäs G, Häyrynen S, Rantapero T, Kivinen V, Isaacs W, Tolonen T, Nykter M, Visakorpi T. Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer. 1shared first authors. Cold Spring Harb Mol Case Stud 2:a000752, 2016.
Latonen L, Scaravilli M, Gillen A, Zhang F, Ruusuvuori P, Kujala P, Poutanen M, Visakorpi T. In vivo expression of miR-32 induces proliferation in prostate epithelium. Am J Pathol, 187:2546-2557, 2017.
Kallio HML, Hieta R, Latonen L, Brofeldt A, Annala M, Kivinummi K, Tammela TL, Nykter M, Isaacs WB, Lilja HG, Bova GS, Visakorpi T
Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases.
Br J Cancer ;119(3)347-356, 2018
Latonen L, Nykter M, Visakorpi T
Proteomics of prostate cancer - revealing how cancer cells master their messy genomes.
Oncoscience ;5(7-8)216-217, 2018
Sainio M, Visakorpi T, Tolonen T, Ilvesaro J, Bova GS
Expression of neuroendocrine differentiation markers in lethal metastatic castration-resistant prostate cancer.
Pathol Res Pract ;214(6)848-856, 2018
Kartasalo K, Latonen L, Vihinen J, Visakorpi T, Nykter M, Ruusuvuori P
Comparative analysis of tissue reconstruction algorithms for 3D histology.
Bioinformatics ;34(17)3013-3021, 2018
Latonen L, Afyounian E, Jylhä A, Nättinen J, Aapola U, Annala M, Kivinummi KK, Tammela TTL, Beuerman RW, Uusitalo H, Nykter M, Visakorpi T
Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression.
Nat Commun ;9(1)1176, 2018
Claessens F, Visakorpi T
Endocrinology of prostate cancer.
Mol Cell Endocrinol ;462(Pt A)1-2, 2018
McNair C, Xu K, Mandigo AC, Benelli M, Leiby B, Rodrigues D, Lindberg J, Gronberg H, Crespo M, De Laere B, Dirix L, Visakorpi T, Li F, Feng FY, de Bono J, Demichelis F, Rubin MA, Brown M, Knudsen KE
Differential impact of RB status on E2F1 reprogramming in human cancer.
J Clin Invest ;128(1)341-358, 2018
Högnäs G, Kivinummi K, Kallio HML, Hieta R, Ruusuvuori P, Koskenalho A, Kesseli J, Tammela TLJ, Riikonen J, Ilvesaro J, Kares S, Hirvikoski PP, Laurila M, Mirtti T, Nykter M, Kujala PM, Visakorpi T, Tolonen T, Bova GS
Feasibility of Prostate PAXgene Fixation for Molecular Research and Diagnostic Surgical Pathology: Comparison of Matched Fresh Frozen, FFPE, and PFPE Tissues.
Am J Surg Pathol ;42(1)103-115, 2018
Kivinummi K, Urbanucci A, Leinonen K, Tammela TLJ, Annala M, Isaacs WB, Bova GS, Nykter M, Visakorpi T
The expression of AURKA is androgen regulated in castration-resistant prostate cancer.
Sci Rep ;7(1)17978, 2017
Assel M, Sjöblom L, Murtola TJ, Talala K, Kujala P, Stenman UH, Taari K, Auvinen A, Vickers A, Visakorpi T, Tammela TL, Lilja H
A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy: An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer.
Eur Urol Focus ;2017
Latonen L, Scaravilli M, Gillen A, Hartikainen S, Zhang FP, Ruusuvuori P, Kujala P, Poutanen M, Visakorpi T
In Vivo Expression of miR-32 Induces Proliferation in Prostate Epithelium.
Am J Pathol ;187(11)2546-2557, 2017
Granberg KJ, Annala M, Lehtinen B, Kesseli J, Haapasalo J, Ruusuvuori P, Yli-Harja O, Visakorpi T, Haapasalo H, Nykter M, Zhang W
Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas.
Neuro Oncol ;19(9)1206-1216, 2017
Urbanucci A, Barfeld SJ, Kytölä V, Itkonen HM, Coleman IM, Vodák D, Sjöblom L, Sheng X, Tolonen T, Minner S, Burdelski C, Kivinummi KK, Kohvakka A, Kregel S, Takhar M, Alshalalfa M, Davicioni E, Erho N, Lloyd P, Karnes RJ, Ross AE, Schaeffer EM, Vander Griend DJ, Knapp S, Corey E, Feng FY, Nelson PS, Saatcioglu F, Knudsen KE, Tammela TLJ, Sauter G, Schlomm T, Nykter M, Visakorpi T, Mills IG
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer.
Cell Rep ;19(10)2045-2059, 2017
Lehtinen B, Raita A, Kesseli J, Annala M, Nordfors K, Yli-Harja O, Zhang W, Visakorpi T, Nykter M, Haapasalo H, Granberg KJ
Clinical association analysis of ependymomas and pilocytic astrocytomas reveals elevated FGFR3 and FGFR1 expression in aggressive ependymomas.
BMC Cancer ;17(1)310, 2017
Valkonen M, Ruusuvuori P, Kartasalo K, Nykter M, Visakorpi T, Latonen L
Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models.
Sci Rep ;2017