Cancers (Feb 2024)
Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer—Insights from Histologically Normal Urothelium
- Wiktoria Stańkowska,
- Daniil Sarkisyan,
- Bożena Bruhn-Olszewska,
- Katarzyna Duzowska,
- Michał Bieńkowski,
- Marcin Jąkalski,
- Magdalena Wójcik-Zalewska,
- Hanna Davies,
- Kinga Drężek-Chyła,
- Rafał Pęksa,
- Agnieszka Harazin-Lechowska,
- Aleksandra Ambicka,
- Marcin Przewoźnik,
- Agnieszka Adamczyk,
- Karol Sasim,
- Wojciech Makarewicz,
- Marcin Matuszewski,
- Wojciech Biernat,
- Josef D. Järhult,
- Miklós Lipcsey,
- Michael Hultström,
- Robert Frithiof,
- Janusz Jaszczyński,
- Janusz Ryś,
- Giulio Genovese,
- Arkadiusz Piotrowski,
- Natalia Filipowicz,
- Jan P. Dumanski
Affiliations
- Wiktoria Stańkowska
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Daniil Sarkisyan
- Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, BMC, Husargatan 3, 751 08 Uppsala, Sweden
- Bożena Bruhn-Olszewska
- Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, BMC, Husargatan 3, 751 08 Uppsala, Sweden
- Katarzyna Duzowska
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Michał Bieńkowski
- Department of Pathomorphology, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Marcin Jąkalski
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Magdalena Wójcik-Zalewska
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Hanna Davies
- Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, BMC, Husargatan 3, 751 08 Uppsala, Sweden
- Kinga Drężek-Chyła
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Rafał Pęksa
- Department of Pathomorphology, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Agnieszka Harazin-Lechowska
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Aleksandra Ambicka
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Marcin Przewoźnik
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Agnieszka Adamczyk
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Karol Sasim
- Clinic of Urology and Oncological Urology, Specialist Hospital of Kościerzyna, Piechowskiego 36, 83-400 Kościerzyna, Poland
- Wojciech Makarewicz
- Clinic of General and Oncological Surgery, Specialist Hospital of Kościerzyna, Piechowskiego 36, 83-400 Kościerzyna, Poland
- Marcin Matuszewski
- Department and Clinic of Urology, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Wojciech Biernat
- Department of Pathomorphology, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Josef D. Järhult
- Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, 751 85 Uppsala, Sweden
- Miklós Lipcsey
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska Sjukhuset, 751 85 Uppsala, Sweden
- Michael Hultström
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska Sjukhuset, 751 85 Uppsala, Sweden
- Robert Frithiof
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska Sjukhuset, 751 85 Uppsala, Sweden
- Janusz Jaszczyński
- Department of Urology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Janusz Ryś
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Garncarska 11, 31-115 Kraków, Poland
- Giulio Genovese
- Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
- Arkadiusz Piotrowski
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Natalia Filipowicz
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- Jan P. Dumanski
- 3P-Medicine Laboratory, Medical University of Gdańsk, M. Sklodowskiej-Curie 3A, 80-210 Gdańsk, Poland
- DOI
- https://doi.org/10.3390/cancers16050961
- Journal volume & issue
-
Vol. 16,
no. 5
p. 961
Abstract
Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.
Keywords
- bladder carcinoma (BLCA)
- cystectomy
- transurethral resection of bladder tumor (TURBT)
- post-zygotic mutations
- normal urothelium
- chromosomal copy number alterations