UNTANGLING MOLECULAR ORIGINS OF COLORECTAL CARCINOMAS AND ASSIGNMENT OF MAJOR PATHWAYS BASED ON CIMP/MSI/BRAF/KRAS/TP53/APC PROFILES FROM ENDOSCOPIC TISSUE SAMPLING

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F26475821%3A_____%2F16%3AN0000029" target="_blank" >RIV/26475821:_____/16:N0000029 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

UNTANGLING MOLECULAR ORIGINS OF COLORECTAL CARCINOMAS AND ASSIGNMENT OF MAJOR PATHWAYS BASED ON CIMP/MSI/BRAF/KRAS/TP53/APC PROFILES FROM ENDOSCOPIC TISSUE SAMPLING

Popis výsledku v původním jazyce

Poster at UEGW2016: Recent advances in molecular profiling have resulted in definition of molecular types of colorectal cancer based on genetic and epigenetic aberrations. Resulting from separate developmental pathways the different types are associated with distinct prognostic features, which can be utilized in clinical practice. The aim of this study was to assign molecular subtypes based on CIN/CIMP/MSI molecular phenotypes in combination with mutation status of (proto)oncogenes KRAS and BRAF and tumor suppressors TP53 and APC in large adenomas and in early and late carcinomas for assessment of patients prognosis. A prospective 3-year study has resulted in the acquisition of samples (fresh biopsies or FFPE sections from EPE or EMR) from 138 carcinomas along with associated clinical parameters including localization, grade and histological type from adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed on endoscopic tissue specimens using methylation-specific multiplex ligation-dependent probe amplification technique (MS-MLPA) for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability (MSI) and high-sensitive CE melting assay for multiplex detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. We have identified carcinomas belonging into 5 major molecular subtypes: (i) 3x serrated CIMP+/BRAF+/MSI-; (ii) 9x serrated CIMP+/BRAF+/MSI+; (iii) 2x familial CIMP+/MSI+/BRAF-, (iv) 38x Traditional CIMP-/KRAS+/APC+ and (v) 18x Traditional CIMP+/TP53+. The remaining 68 carcinomas were resulting from other combinations. The complex molecular profiling using combination of phenotypes with somatic mutations of oncogenes and tumor supressors allows for efficient stratification of carcinomas with subsequent assignment of prognosis.

Název v anglickém jazyce

UNTANGLING MOLECULAR ORIGINS OF COLORECTAL CARCINOMAS AND ASSIGNMENT OF MAJOR PATHWAYS BASED ON CIMP/MSI/BRAF/KRAS/TP53/APC PROFILES FROM ENDOSCOPIC TISSUE SAMPLING

Popis výsledku anglicky

Poster at UEGW2016: Recent advances in molecular profiling have resulted in definition of molecular types of colorectal cancer based on genetic and epigenetic aberrations. Resulting from separate developmental pathways the different types are associated with distinct prognostic features, which can be utilized in clinical practice. The aim of this study was to assign molecular subtypes based on CIN/CIMP/MSI molecular phenotypes in combination with mutation status of (proto)oncogenes KRAS and BRAF and tumor suppressors TP53 and APC in large adenomas and in early and late carcinomas for assessment of patients prognosis. A prospective 3-year study has resulted in the acquisition of samples (fresh biopsies or FFPE sections from EPE or EMR) from 138 carcinomas along with associated clinical parameters including localization, grade and histological type from adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed on endoscopic tissue specimens using methylation-specific multiplex ligation-dependent probe amplification technique (MS-MLPA) for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability (MSI) and high-sensitive CE melting assay for multiplex detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. We have identified carcinomas belonging into 5 major molecular subtypes: (i) 3x serrated CIMP+/BRAF+/MSI-; (ii) 9x serrated CIMP+/BRAF+/MSI+; (iii) 2x familial CIMP+/MSI+/BRAF-, (iv) 38x Traditional CIMP-/KRAS+/APC+ and (v) 18x Traditional CIMP+/TP53+. The remaining 68 carcinomas were resulting from other combinations. The complex molecular profiling using combination of phenotypes with somatic mutations of oncogenes and tumor supressors allows for efficient stratification of carcinomas with subsequent assignment of prognosis.

Druh

O - Ostatní výsledky

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/NT14383" target="_blank" >NT14383: Využití volné nádorové DNA jako nového cíle pro minimálně-invazivní diagnostiku a zpřesnění molekulární klasifikace kolorektálních nádorů.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů