December 2023 - Tanja Limberger

Dipl.-Ing. Tanja Limberger

MedUni Wien RESEARCHER OF THE MONTH December 2023

Prostate cancer ranks among the most frequently diagnosed malignancies in men and results in more than 375.000 deaths per year. Even though the stratification of localized prostate cancers into slow-progressing and aggressive tumours is highly relevant for optimal treatment regimen selection, there is still a lack of reliable prognostic markers. Recent studies have shown that the epigenetic regulator KMT2C is frequently mutated in prostate cancers, yet the impact of these mutations on tumorigenesis had not yet been elucidated.

In their study, Dipl.-Ing.ⁱⁿ Tanja Limberger and colleagues used a transgenic mouse model of prostate cancer and previously published sequencing data from a large cohort of patients to show that loss-of-function mutations in KMT2C promote the proliferation and metastatic progression of prostate tumours by inhibiting the expression of the cell cycle repressor p16^INK4A. Thus, their work provides novel insights into the as yet poorly understood switch from localized to metastatic prostate cancer and identifies mutated forms of KMT2C as a potential marker for high-risk prostate cancer.

Selected Literature

1. Limberger, T., et al., KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis. Mol Cancer, 2022. 21(1): p. 89.

2. Siegel, R.L., et al., Cancer statistics, 2022. CA Cancer J Clin, 2022. 72(1): p. 7-33.

3. Rebello, R.J., et al., Prostate cancer. Nat Rev Dis Primers, 2021. 7(1): p. 9.

4. Armenia, J., et al., The long tail of oncogenic drivers in prostate cancer. Nat Genet, 2018. 50(5): p. 645-651.

5. Rao, R.C. and Y. Dou, Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat Rev Cancer, 2015. 15(6): p. 334-46.

6. Oberhuber, M., et al., STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer. Mol Syst Biol, 2020. 16(4): p. e9247.

7. Garces de Los Fayos Alonso, I., et al., PDGFRbeta promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma. Mol Cancer, 2022. 21(1): p. 172.

8. Prutsch, N., et al., Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma. Leukemia, 2019. 33(3): p. 696-709.

   Publication list of the first author

   		IF	Year
   1.	KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis. Limberger T, Schlederer M, Trachtová K, Garces de Los Fayos Alonso I, Yang J, Högler S, Sternberg C, Bystry V, Oppelt J, Tichý B, Schmeidl M, Kodajova P, Jäger A, Neubauer HA, Oberhuber M, Schmalzbauer BS, Pospisilova S, Dolznig H, Wadsak W, Culig Z, Turner SD, Egger G, Lagger S, Kenner L.; Molecular Cancer	41.44	2022
   2.	PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma. Garces de Los Fayos Alonso I, Zujo L, Wiest I, Kodajova P, Timelthaler G, Edtmayer S, Zrimšek M, Kollmann S, Giordano C, Kothmayer M, Neubauer HA, Dey S, Schlederer M, Schmalzbauer BS, Limberger T, Probst C, Pusch O, Högler S, Tangermann S, Merkel O, Schiefer AI, Kornauth C, Prutsch N, Zimmerman M, Abraham B, Anagnostopoulos J, Quintanilla-Martinez L, Mathas S, Wolf P, Stoiber D, Staber PB, Egger G, Klapper W, Woessmann W, Look TA, Gunning P, Turner SD, Moriggl R, Lagger S, Kenner L.; Molecular Cancer	41.44	2022
   3.	STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer. Oberhuber M, Pecoraro M, Rusz M, Oberhuber G, Wieselberg M, Haslinger P, Gurnhofer E, Schlederer M, Limberger T, Lagger S, Pencik J, Kodajova P, Högler S, Stockmaier G, Grund-Gröschke S, Aberger F, Bolis M, Theurillat JP, Wiebringhaus R, Weiss T, Haitel A, Brehme M, Wadsak W, Griss J, Mohr T, Hofer A, Jäger A, Pollheimer J, Egger G, Koellensperger G, Mann M, Hantusch B, Kenner L.; Molecular Systems Biology	11.43	2020
   4.	Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma. Prutsch N, Gurnhofer E, Suske T, Liang HC, Schlederer M, Roos S, Wu LC, Simonitsch-Klupp I, Alvarez-Hernandez A, Kornauth C, Leone DA, Svinka J, Eferl R, Limberger T, Aufinger A, Shirsath N, Wolf P, Hielscher T, Sternberg C, Aberger F, Schmoellerl J, Stoiber D, Strobl B, Jäger U, Staber PB, Grebien F, Moriggl R, Müller M, Inghirami GG, Sanda T, Look AT, Turner SD, Kenner L, Merkel O.; Leukemia	11.53	2019