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Molecular changes d...
Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma
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- Sjödahl, Gottfrid (author)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Eriksson, Pontus (author)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Patschan, Oliver (author)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urology - urothelial cancer, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Marzouka, Nour Al Dain (author)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Jakobsson, Lovisa (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Bernardo, Carina (author)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lövgren, Kristina (author)
- Lund University,Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,The Liquid Biopsy and Tumor Progression in Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Chebil, Gunilla (author)
- Unilabs AB
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- Zwarthoff, Ellen (author)
- Erasmus University Medical Center
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- Liedberg, Fredrik (author)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urology - urothelial cancer, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Höglund, Mattias (author)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
- 2019-11-14
- 2020
- English 12 s.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:9, s. 2636-2647
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Abstract
Subject headings
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- Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- bladder cancer
- molecular subtypes
- mutation
- progression
- urothelial carcinoma
Publication and Content Type
- art (subject category)
- ref (subject category)
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Sjödahl, Gottfri ...
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Eriksson, Pontus
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Patschan, Oliver
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Marzouka, Nour A ...
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Jakobsson, Lovis ...
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Bernardo, Carina
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Lövgren, Kristin ...
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Chebil, Gunilla
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Zwarthoff, Ellen
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Liedberg, Fredri ...
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Höglund, Mattias
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