Detection of IDH1 and IDH2 somatic mutations in brain tumors by denaturing capillary electrophoresis (DCE)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F26475821%3A_____%2F15%3AN0000004" target="_blank" >RIV/26475821:_____/15:N0000004 - 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

Detection of IDH1 and IDH2 somatic mutations in brain tumors by denaturing capillary electrophoresis (DCE)

Popis výsledku v původním jazyce

Poster at Helsinki ITP2015: Malignant gliomas representing the most frequent type of brain cancer are among the worse in prognosis among solid cancers. The most critical are high grade glioblastomas exhibiting high malignancy whose median of survival is typically between 12 and 24 months from diagnosis. Malignant transformation is frequently supplemented by somatic mutations in Isocitrate dehydrogenase 1 and 2 genes (IDH1, IDH2), both involved in energy metabolism . It has recently emerged that IDH1/2 mutations are associated with prolonged survival and should be used as prognostic factor in management of brain cancer patients . There are several approaches currently in use for the detection of IDH1/2 mutations including allele-specific PCR, high-resolution melting and MLPA . While currently often used in clinical settings, these techniques exhibit various shortcomings including complex protocols (multiple pipetting steps required), high sample demand (amounts of input DNA required) and long processing time. A simple and rapid method would therefore be highly desired. Aims: To develop IDH1/2 mutation detection assay using denaturing capillary electrophoresis approach and perform a validation against a reference technology that is currently in use. Results: Following optimization steps a total of 61 tumor samples were examined revealing IDH1 mutation in 20 cases (32.7%), IDH2 mutation in 1 case (1.6%) and MGMT promotor methylation in 27 cases (44.2%). There was a 100% concordance in IDH1/2 mutation results between the newly developed DCE approach and MLPA. Conclusions: A combination of fragment analysis and denaturing CE modes is suitable for molecular testing of brain gliomas easily implementable in clinical oncology practice.

Název v anglickém jazyce

Detection of IDH1 and IDH2 somatic mutations in brain tumors by denaturing capillary electrophoresis (DCE)

Popis výsledku anglicky

Poster at Helsinki ITP2015: Malignant gliomas representing the most frequent type of brain cancer are among the worse in prognosis among solid cancers. The most critical are high grade glioblastomas exhibiting high malignancy whose median of survival is typically between 12 and 24 months from diagnosis. Malignant transformation is frequently supplemented by somatic mutations in Isocitrate dehydrogenase 1 and 2 genes (IDH1, IDH2), both involved in energy metabolism . It has recently emerged that IDH1/2 mutations are associated with prolonged survival and should be used as prognostic factor in management of brain cancer patients . There are several approaches currently in use for the detection of IDH1/2 mutations including allele-specific PCR, high-resolution melting and MLPA . While currently often used in clinical settings, these techniques exhibit various shortcomings including complex protocols (multiple pipetting steps required), high sample demand (amounts of input DNA required) and long processing time. A simple and rapid method would therefore be highly desired. Aims: To develop IDH1/2 mutation detection assay using denaturing capillary electrophoresis approach and perform a validation against a reference technology that is currently in use. Results: Following optimization steps a total of 61 tumor samples were examined revealing IDH1 mutation in 20 cases (32.7%), IDH2 mutation in 1 case (1.6%) and MGMT promotor methylation in 27 cases (44.2%). There was a 100% concordance in IDH1/2 mutation results between the newly developed DCE approach and MLPA. Conclusions: A combination of fragment analysis and denaturing CE modes is suitable for molecular testing of brain gliomas easily implementable in clinical oncology practice.

Druh

O - Ostatní výsledky

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/NT14253" target="_blank" >NT14253: Epigenetické markery ovlivňující chování mozkových nádorů</a><br>

Návaznosti

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

Rok uplatnění

2015

Kód důvěrnosti údajů

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