Tissue architecture delineates field cancerization in BRAFV600E-induced tumor development
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F22%3A00082396" target="_blank" >RIV/00023001:_____/22:00082396 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/22:10442769
Result on the web
<a href="https://journals.biologists.com/dmm/article/15/2/dmm048887/271800/Tissue-architecture-delineates-field-cancerization" target="_blank" >https://journals.biologists.com/dmm/article/15/2/dmm048887/271800/Tissue-architecture-delineates-field-cancerization</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1242/dmm.048887" target="_blank" >10.1242/dmm.048887</a>
Alternative languages
Result language
angličtina
Original language name
Tissue architecture delineates field cancerization in BRAFV600E-induced tumor development
Original language description
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 BRAF- mutant 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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30109 - Pathology
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Disease Models and Mechanisms
ISSN
1754-8403
e-ISSN
1754-8411
Volume of the periodical
15
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
"Art. no. dmm048887"
UT code for WoS article
000767197800001
EID of the result in the Scopus database
2-s2.0-85113846120