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Tissue architecture...
Tissue architecture delineates field cancerization in brafv600e-induced tumor development
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- Schoultz, Elin (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Sahlgrenska Center for Cancer Research (SCCR)
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- Johansson, Ellen (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Moccia, Carmen (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Jakubikova, Iva (author)
- Charles University in Prague
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- Ravi, Naveen (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
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- Liang, Shawn, 1981 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Carlsson, Therese, 1968 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Sahlgrenska Center for Cancer Research (SCCR)
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- Montelius, Mikael, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för radiologi,Institute of Clinical Sciences, Department of Radiology,Sahlgrenska Academy
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- Patyra, Konrad (author)
- University of Turku
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- Kero, Jukka (author)
- University of Turku
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- Paulsson, Kajsa (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Aneuploidy in cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Fagman, Henrik, 1975 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Sahlgrenska Center for Cancer Research (SCCR),Sahlgrenska University Hospital
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- Bergo, Martin O. (author)
- Karolinska Institute
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- Nilsson, Mikael, 1958 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Sahlgrenska Center for Cancer Research (SCCR)
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(creator_code:org_t)
- 2022
- 2022
- English.
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In: DMM Disease Models and Mechanisms. - 1754-8403 .- 1754-8411. ; 15:2
- Related links:
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Abstract
Subject headings
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- Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAFmutant lineage becomes a cancerized lineage. The TgCreERT2; BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Braf mutation
- Cancer
- Development
- Oligoclonal
- Oncogenic activation
- Thyroid
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Schoultz, Elin
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Johansson, Ellen
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Moccia, Carmen
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Jakubikova, Iva
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Ravi, Naveen
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Liang, Shawn, 19 ...
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show more...
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Carlsson, Theres ...
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Montelius, Mikae ...
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Patyra, Konrad
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Kero, Jukka
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Paulsson, Kajsa
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Fagman, Henrik, ...
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Bergo, Martin O.
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Nilsson, Mikael, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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DMM Disease Mode ...
- By the university
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University of Gothenburg
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Lund University