The department is focused on research into the molecular characteristics of cancer, especially of the colon and rectum. Within these studies we focus on the molecular epidemiological level in order to identify biomarkers of increased predisposition to tumor diseases, enable early diagnostics, assess individual responses to anti‑tumor treatment, and determine the long-term prognosis. The department has been working with different types of biological material from patients with cancer diseases, such as solid tissue, blood cells, plasma and stool.
Head of the Department
Veronika Vymetálková, Ph.D.
Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition
To dissect the genetics in the evolvement of colorectal adenomas into colorectal carcinomas (CRC) we have analyzed the mutation spectrum of genes involved in CRC (APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, TP53) in 96 adenomas and in situ carcinomas by a high-throughput genotyping technique. We found a high frequency of pathogenic variants in these genes. The APC, KRAS and TP53 mutation frequencies were lower in adenomas than in in situ carcinoma samples. The frequency distribution of mutations was as follows: low-grade adenomas-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. KRAS mutations occurred mainly in villous histology, APC promoter methylation associated with POLE genetic variations. There is a multistep model of gradual accumulation of mutations in the driver genes.
The distribution of genetic alterations detected in low-grade, high-grade adenomas, and in situ carcinomas. Each row represents a patient, and each column represents a gene. Different mutation types are indicated by different colors. The bar chart on the top shows the total number of the given gene’s mutations observed in the sample.
Publication:
Jungwirth, J., Urbanová, M., Boot, A., Hošek, P., Bendová, P., Šišková, A., Švec, J., Kment, M., Tůmová, D., Summerová, S., Beneš, Z., Buchler, T., Kohout, P., Hucl, T., Matěj, R., Vodičková, L., van Wezel, T., Vodička, P., Vymetálková, V.: (2022) Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition. Scientific Reports. 12(1): 2570. doi: 10.1038/s41598-022-06498-9.
Analysis of microRNA expression changes during the course of therapy in rectal cancer patients
MicroRNAs (miR) regulate gene expression in a tissue-specific manner. However, little is known about the miR expression changes during the therapy in rectal cancer (RC) patients. Here the expression levels of miR-122-5p and miR-142-5p were significantly different between RC patients and controls (p < 0.001). A year after diagnosis, miR expression profiles were no longer different in patients responding to treatment from those measured in cancer-free individuals. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling. Overexpression of miR-122-5p and miR-142-5p in RC cell lines inhibited cell growth and survival. This study shows the usefulness of circulating miR-122-5p and miR-142-5p screening for the assessment of patients’ outcomes and the effectiveness of the treatment schedule.
Expression analysis of miR-122-5p and miR-142-5p in plasma. Expression levels of miR-122-5p and miR-142-5p were significantly lower in plasma from RC patients compared to the plasma of cancer-free individuals. A year from the diagnosis (2nd sampling, T1), a significant difference was observed between patients that do not respond a year after diagnosis and cancer-free individuals.
Publication:
Červená, K., Novosadová, V., Pardini, B., Naccarati, A., Opattová, A., Horák, J., Vodenková, S., Buchler, T., Skrobanek, P., Levy, M., Vodička, P., Vymetálková, V.: (2021) Analysis of MicroRNA Expression Changes During the Course of Therapy In Rectal Cancer Patients. Frontiers in Oncology. 11: 702258. doi: 10.3389/fonc.2021.702258. eCollection 2021
Projects
1. 5. 2021 – 31. 12. 2024
Telomere homeostasis as potential biomerker of risk, prognosis and progression in gyneacologic tumours
mikroRNA a onkogenní KRAS mutace pro stanovení včasné diagnózy a zhodnocení rizika vzniku karcinomu pankreatu. Concept of liquid biopsy in mapping of microRNA and oncogenicKRAS mutations for early diagnosis and risk assessment of pancreatic cancer
Department of Molecular Biology of CancerCorradi C.Lencioni G.Felici A.Rizzato C.Gentiluomo M.Ermini S.Archibugi L.Mickevicius A.Lucchesi M.Malecka-Wojciesko E....Červená K....Pezzilli R.Sperti C.Kauffmann E.Büchler M. W.Schöttker B.Hegyi P.Capretti G.Lawlor R. T.Canzian F.Campa D.
2024
Int J Cancer . 2024 Oct 15;155(8):1432-1442. doi: 10.1002/ijc.35046. Epub 2024 Jun 26.
Department of Molecular Biology of CancerSchormair B.Zhao Ch.Bell S.Didriksen M.Nawaz M. S.Schandra N.Stefani A.Högl B.Dauvilliers Y.Bachmann C. G.Kemlink D.Sonka K.Paulus W.Trenkwalder C.Oertel W. H.Hornyak M.Teder-Laving M.Metspalu A.Hadjigeorgiou G. M.Polo O.Fietze I.Ross O. A.Wszolek Z. K.Ibrahim A.Bergmann M.Kittke V.Harrer P.Dowsett J.Chenini S.Ostrowski S. R.Sørensen E.Erikstrup C.Pedersen O. B.Bruun M. T.Nielsen K. R.Butterworth A. S.Soranzo N.Ouwehand W. H.Roberts D. J.Danesh J.Burchell B.Furlotte N. A.Nandakumar P.Earley C. J.Ondo W. G.Xiong L.Desautels A.Perola M.Vodička P.Dina C.Stoll M.Franke A.Lieb W.Stewart A. F. R.Shah S. H.Gieger C.Peters A.Rye D. B.Rouleau G. A.Berger K.Stefansson H.Ullum H.Stefansson K.Hinds D. A.Di Angelantonio E.Oexle K.Winkelmann J.
2024
Nat Genet . 2024 Jun;56(6):1090-1099. doi: 10.1038/s41588-024-01763-1. Epub 2024 Jun 5.
Department of Molecular Biology of CancerManrique-Silva E.David M.-E.Maider A.-M.García-Casado Z.Moro R.Requena C.Través V.Virós A.R. KumarNagore E.
2024
Pigment Cell Melanoma Res . 2024 May;37(3):343-351. doi: 10.1111/pcmr.13155. Epub 2023 Dec 28.
Department of Molecular Biology of CancerChen Z.Guo X.Tao R.Huyghe J. R.Law P. J.Fernandez-Rozadilla C.Ping J.Jia G.J. LongLi C....Vodička P.Vodičková L.Vymetálková V....Hsu L.Cai Q.Dunlop M. G.Gruber S. B.Houlston R. S.Moreno V.Casey G.Peters U.Tomlinson I.Zheng W.
2024
Nat Commun . 2024 Apr 26;15(1):3557. doi: 10.1038/s41467-024-47399-x.
Department of Molecular Biology of CancerÜnal P.Lu Y.Bueno-de-Mesquita B.van Eijck C. H. J.Talar-Wojnarowska R.Szentesi A.Gazouli M.Kreivenaite E.Tavano F.Małecka-Wojciesko E....Vodičková L....Červená K.Pasquali C. Lawlor R. T.Bazzocchi F.Kupcinskas J.Capurso G.Campa D.Canzian F.
2024
Hum Genomics . 2024 Feb 2;18(1):12. doi: 10.1186/s40246-024-00576-x.
Department of Molecular Biology of CancerGiaccherini M.Gori L.Gentiluomo M.Farinella R.Červená K.Skieceviciene J.Dijk F.Capurso G.Vezakis A.Archibugi L....van Laarhoven H. W. M.Soucek P.Götz M.Erőss B.Cavestro G. M.Basso D.Perri F.Landi S.Canzian F.Campa D.
2023
Carcinogenesis . 2023 Dec 2;44(8-9):642-649. doi: 10.1093/carcin/bgad056.
Department of Molecular Biology of CancerNodari Y.Gentiluomo M.Mohelnikova-Duchonova B.Kreivenaite E.Milanetto A. C.Skieceviciene J.Landi S.Lawlor R. T.Petrone M. C.Arcidiacono P. G....Vodička P....Capurso G.Perri F.Ermini S.Theodoropoulos G.Capretti G.Palmieri O.Ginocchi L.Furbetta N.Canzian F.Campa D.
2023
Dig Liver Dis . 2023 Oct;55(10):1417-1425. doi: 10.1016/j.dld.2023.02.023. Epub 2023 Mar 25.
Department of Molecular Biology of CancerThomas M.Qu C.Wang X.Huyghe J. R.Joo J. E.Georgeson P.Arndt V.Berndt S. I.Bézieau S.Bien S. A.Bishop D. T.Brenner H.Brezina S.Burnett-Hartman A.Campbell P. T.Casey G.Castellví-Bel S.Chan A. T.Chang-Claude J.Chen X.Conti D. V.Cremolini C.Diergaarde B.Figueiredo J. C.FitzGerald L. M.Gago-Dominguez M.Gallinger S.Giles G. G.Gsu A.Gunter M. J.Hampe J.Hampel H.Harrison T. A.Hoffmeister M.Keku T. O.Kundaje A.Le Marchand L.Lenz H.-J.Li C. I.Li L.Lin Y.Lindblom A.Moreno V.Murphy N.Newcomb P. A.Newton C. C.Obón-Santacana M.Ogino S.Pai R. K.Palmer J. R.Pearlman R.Pharoah P. D. P.Phipps A. I.Platz E. A.Potter J. D.Rennert G.Sakoda L. C.Schafmayer C.Schmit S. L.Schoen R. E.Slattery M. L.Stadler Z. K.Steinfelder R. S.Thibodeau S. N.Ulrich C. M.Um C. Y.van Duijnhoven F. J. B.Van Guelpen B.Visvanathan K.Vodička P.Vodičková L.Vymetálková V.Weinstein S. J.White E.Winship I. M.Wolk A.Gruber S. B.Jenkins M. A.Hsu L.Buchanan D. D.Peters U.
2023
Gastroenterology. 2023 Oct;165(4):1070-1076.e3. doi: 10.1053/j.gastro.2023.06.032. Epub 2023 Jul 14.
Department of Molecular Biology of CancerThomas M.Su Y-R.Rosenthal E. A.Sakoda L. C.Schmit S. L.Timofeeva M. N.Chen Z.Fernandez-Rozadilla C.Law P. J.Murphy N.Carreras-Torres R.Diez-Obrero V.van Duijnhoven F. J. B.Jiang S.Shin A.Wolk A.Phipps A. I.Burnett-Hartman A.Gsur A.Chan A. T.Zauber A. G.Wu A. H.Lindblom A.Um C. Y.Tangen C. M.Gignoux C.Newton C.Haiman C. A.Qu C.Bishop D. T.Buchanan D. D.Crosslin D. R.Conti D. V.Kim D-H.Hauser E.White E.Siegel E.Schumacher F. R.Rennert G.Giles G. G.Hampel H.Brenner H.Oze I.Oh J. H.Lee J. K.Schneider J. L.Chang-Claude J.Kim J.Huyghe J. R.Zheng J.Hampe J.Greenson J.Hopper J. L.Palmer J. R.Visvanathan K.Matsuo K.Matsuda K.Jung K. J.Li L.Le Marchand L.Vodičková L.Bujanda L.Gunter M. J.Matejcic M.Jenkins M. A.Slattery M. L.D'Amato M.Wang M.Hoffmeister M.Woods M. O.Kim M.Song M.Iwasaki M.Du M.Udaltsova N.Sawada N.Vodička P.Campbell P. T.Newcomb P. A.Cai Q.Pearlman R.Pai R. K.Schoen R. E.Steinfelder R. S.Haile R. W.Vandenputtelaar R.Prentice R. L.Küry S.Castellví-Bel S.Tsugane S.Berndt S. I.Lee S. C.Brezina S.Weinstein S. J.Chanock S. J.Jee S. H.Kweon S-S.Vadaparampil S.Harrison T. A.Yamaji T.Keku T. O.Vymetálková V.Arndt V.Jia W-H.Shu X-O.Lin Y.Ahn Y-O.Stadler Z. K.Van Guelpen B.Ulrich C. M.Platz E. A.Potter J. D.Li C. I.Meester R.Moreno V.Figueiredo J. C.Casey G.Lansdorp Vogelaar I.Dunlop M. G.Gruber S. B.Hayes R. B.Pharoah P. D.Houlston R. S.Jarvik G. P.Tomlinson I. P.Zheng W.Corley D. A.Peters U.Hsu L.
2023
Nat Commun. 2023 Oct 2;14(1):6147. doi: 10.1038/s41467-023-41819-0.
Department of Molecular Biology of CancerDimou N.Kim A. E.Flanagan O.Murphy N.Diez-Obrero V.Shcherbina A.Aglago E. K.Bouras E.Campbell P. T.Casey G....Vodička P.Vodičková L.White E.Wolk A.Woods M. O.Qu C.Kundaje A.Hsu L.Gauderman W. J.Gunter M. J.Peters U.
2023
Br J Cancer . 2023 Aug;129(3):511-520. doi: 10.1038/s41416-023-02312-z. Epub 2023 Jun 26.
Department of Molecular Biology of CancerAglago E. K.Kim A. E.Lin Y.Qu C.Evangelou M.Ren Y.Morrison J.Albanes D.Arndt V.Barry E. L.Baurley J. W.Berndt S. I.Bien S. A.Bishop D. T.Bouras E.Brenner H.Buchanan D. D.Budiarto A.Carreras-Torres R.Casey G.Cenggoro T. W.Chan A. T.Chang-Claude J.Chen X.Conti D. V.Devall M.Díez-Obrero V.Dimou N.Drew D.Figueiredo J. C.Gallinger S.Giles G. G.Gruber S. B.Gsur A.Gunter M. J.Hampel H.Harlid S.Hidaka A.Harrison T. A.Hoffmeister M.Huyghe J. R.Jenkins M. A.Jordahl K.Joshi A. D.Kawaguchi E. S.Keku T. O.Kundaje A.Larsson S. C.Le Marchand L.Lewinger J. P.Li L.Lynch B. M.Mahesworo B.Mandic M.Obón-Santacana M.Moreno V.Murphy N.Nan H.Nassir R.Newcomb P. A.Ogino S.Ose J.Pai R. K.Palmer J. R.Papadimitriou N.Pardamean B.Peoples A. R.Platz E. A.Potter J. D.Prentice R. L.Rennert G.Ruiz-Narvaez E.Sakoda L. C.Scacheri P. C.Schmit S. L.Schoen R. E.Shcherbina A.Slattery M. L.Stern M. C.Su Y. R.Tangen C. M.Thibodeau S. N.Thomas D. C.Tian Y.Ulrich C. M.van Duijnhoven F. J. B.Van Guelpen B.Visvanathan K.Vodička P.Wang J.White E.Wolk A.Woods M. O.Wu A. H.Zemlianskaia N.Hsu L.Gauderman W. J.Peters U.Tsilidis K. K.Campbell P. T.
2023
Cancer Res . 2023 May 30;CAN-22-3713. doi: 10.1158/0008-5472.CAN-22-3713. Online ahead of print.
Department of Molecular Biology of CancerTsilidis K. K.Papadimitriou N.Dimou N.Gill D.Lewis S. J.Martin R. M.Murphy N.Markozannes G.Zuber V.Cross A. J.Burrows K.Lopez D. S.Key T. J.Travis R. C.Perez-Cornago A.Hunter D. J.van Duijnhoven F. J. B.Albanes D.Arndt V.Berndt S. I.Bézieau S.Bishop D. T.Boehm J.Brenner H.Burnett-Hartman A.Campbell P. T.Casey G.Castellví-Bel S.Chan A. T.Chang-Claude J.de la Chapelle A.Figueiredo J. C.Gallinger S. J.Giles G. G.Goodman P. J.Gsur A.Hampe J.Hampel H.Hoffmeister M.Jenkins M. A.Keku T. O.Kweon S.-S.Larsson S. C.Le Marchand L.Li C. I.Li L.Lindblom A.Martín V.Milne R. L.Moreno V.Nan H.Nassir R.Newcomb P. A.Offit K.Pharoah P. D. P.Platz E. A.Potter J. D.Qi L.Rennert G.Sakoda L. C.Schafmayer C.Slattery M. L.Snetselaar L.Schenk J.Thibodeau S. N.Ulrich C. M.Van Guelpen B.Harlid S.Visvanathan K.Vodičková L.Wang H.White E.Wolk A.Woods M. O.Wu A. H.Zheng W.Bueno-de-Mesquita B.Boutron-Ruault M.-C.Hughes D. J.Jakszyn P.Kühn T.Palli D.Riboli E.Giovannucci E. L.Banbury B. L.Gruber S. B.Peters U.Gunter M. J.
2021
Journal of Clinical Nutrition. 113(6): 1490-1502.
Department of Molecular Biology of CancerLu Y.Gentiluomo M.Gioffreda D.Gazouli M.Petrone M. C.Kelemen D.Ginocchi L.Morelli L.Papiris K.Greenhalf W.Izbicki J. R.Kiudelis V.Mohelníková-Duchoňová B.Bueno-de-Mesquita B.Vodička P.Brenner H.Diener M. K.Pezzilli R.Ivanauskas A.Salvia R.Szentesi A.Aoki M. N.Németh B. C.Sperti C.Jamroziak K.Chammas R.Oliverius M.Archibugi L.Ermini S.Novák J.Kupcinskas J.Strouhal O.Souček P.Cavestro G. M.Milanetto A. C.Vanella G.Neoptolemos J. P.Theodoropoulos G. E.van Laarhoven H. W. M.Mambrini A.Moz S.Kala Z.Loveček M.Basso D.Uzunoglu F. G.Hackert T.Testoni S. G. G.Hlaváč V.Andriulli A.Lucchesi M.Tavano F.Carrara S.Hegyi P.Arcidiacono P. G.Busch O. R.Lawlor R. T.Puzzono M.Boggi U.Guo F.Małecka-Panas E.Capurso G.Landi S.Talar-Wojnarowska R.Strobel O.Gao X.Vashist Y.Campa D.Canzian F.
2021
Frontiers in Oncology. 11: 771312.
Department of Molecular Biology of CancerThomas M.Sakoda L. C.Hoffmeister M.Rosenthal E. A.Lee J. K.van Duijnhoven F. J. B.Platz E. A.Wu A. H.Dampier C. H.de la Chapelle A.Wolk A.Joshi A. D.Burnett-Hartman A.Gsur A.Lindblom A.Castells A.Win A. K.Namjou B.Van Guelpen B.Tangen C. M.He Q.Li C. I.Schafmayer C.Joshu C. E.Ulrich C. M.Bishop D. T.Buchanan D. D.Schaid D.Drew D. A.Muller D. C.Duggan D.Crosslin D. R.Albanes D.Giovannucci E. L.Larson E.Qu F.Mentch F.Giles G. G.Hakonarson H.Hampel H.Stanaway I. B.Figueiredo J. C.Huyghe J. R.Minnier J.Chang-Claude J.Hampe J.Harley J. B.Visvanathan K.Curtis K. R.Offit K.Li L.Le Marchand L.Vodickova L.Gunter M. J.Jenkins M. A.Slattery M. L.Lemire M.Woods M. O.Song M.Murphy N.Lindor N. M.Dikilitas O.Pharoah P. D. P.Campbell P. T.Newcomb P. A.Milne R. L.MacInnis R. J.Castellví-Bel S.Ogino S.Berndt S. I.Bézieau S.Thibodeau S. N.Gallinger S. J.Zaidi S. H.Harrison T. A.Keku T. O.Hudson T. J.Vymetálková V.Moreno V.Martín V.Arndt V.Wei W.-Q.Chung W.Su Y.-R.Hayes R. B.White E.Vodička P.Casey G.Gruber S. B.Schoen R. E.Chan A. T.Potter J. D.Brenner H.Jarvik G. P.Corley D. A.Peters U.Hsu L.
2020
American Journal of Human Genetics. 107(3): 432-444.
Department of Molecular Biology of CancerPeduzzi G.Gentiluomo M.Tavano F.Arcidiacono P. G.Ermini S.Vodička P.Boggi U.Cavestro G. M.Capurso G.Morelli L.Milanetto A. C.Pezzilli R.Lawlor R. T.Carrara S.Lovecek M.Souček P.Guo F.Hackert T.Uzunoğlu F. G.Gazouli M.Párniczky A.Kupcinskas J.Bijlsma M. F.Bueno-de-Mesquita B.Vermeulen R.van Eijck C. H. J.Jamroziak K.Talar-Wojnarowska R.Greenhalf W.Gioffreda D.Petrone M. C.Landi S.Archibugi L.Puzzono M.Funel N.Sperti C.Piredda M. L.Mohelnikova-Duchonova B.Lu Y.Hlaváč V.Gao X.Schneider M.Izbicki J. R.Theodoropoulos G. E.Bunduc S.Kreivenaite E.Busch O. R.Małecka-Panas E.Costello E.Perri F.Testoni S. G. G.Vanella G.Pasquali C.Oliverius M.Brenner H.Loos M.Götz M.Georgiou K.Erőss B.Maiello E.Szentesi A.Bazzocchi F.Basso D.Neoptolemos J. P.Hegyi P.Kiudelis V.Canzian F.Campa D.
2021
Cancer Epidemiology Biomarkers & Prevention. 30 (12): 2342-2345.
Department of Molecular Biology of CancerLu Y.Corradi C.Gentiluomo M.López de Maturana E.Theodoropoulos G. E.Roth S.Maiello E.Morelli L.Archibugi L.Izbicki J. R.Sarlós P.Kiudelis V.Oliverius M.Nóbrega Aoki M.Vashist Y.van Eijck C. H. J.Gazouli M.Talar-Wojnarowska R.Mambrini A.Pezzilli R.Bueno-de-Mesquita B.Hegyi P.Souček P.Neoptolemos J. P.Di Franco G.Sperti C.Kauffmann E. F.Hlaváč V.Uzunoğlu F. G.Ermini S.Małecka-Panas E.Lucchesi M.Vanella G.Dijk F.Mohelníková-Duchoňová B.Bambi F.Petrone M. C.Jamroziak K.Guo F.Kolarova K.Capretti G.Milanetto A. C.Ginocchi L.Loveček M.Puzzono M.van Laarhoven H. W. M.Carrara S.Ivanauskas A.Papiris K.Basso D.Arcidiacono P. G.Izbéki F.Chammas R.Vodička P.Hackert T.Pasquali C.Piredda M. L.Costello-Goldring E.Cavestro G. M.Szentesi A.Tavano F.Włodarczyk B.Brenner H.Kreivenaite E.Gao X.Bunduc S.Vermeulen R. C. H.Schneider M. A.Latiano A.Gioffreda D.Testoni S. G. G.Kupcinskas J.Lawlor R. T.Capurso G.Malats N.Campa D.Canzian F.
2021
Frontiers in Genetics. 12: 693933.
Department of Molecular Biology of CancerMurphy N.Song M.Papadimitriou N.Carreras-Torres R.Langenberg C.Martin R.M.Tsilidis K.K.Barroso I.Chen J.Frayling T.Bull C.J.Vincent E.E.Cotterchio M.Gruber S.B.Pai R.K.Newcomb P.A.Perez-Cornago A.van Duijnhoven F.J.B.Van Guelpen B.Vodička P.Wolk A.Wu A.H.Peters U.Chan A.T.Gunter M.
2022
JNCI-Journal of the National Cancer Institute. 114(5): 740-752.