Mutace isocitrátdehydrogenázy jsou lepší prognostický marker než metylace promotoru O⁶-metylguanin-DNA-metyltransferázy u glioblastomů – retrospektivní molekulárně genetická studie gliomů z jednoho centra

English version

Authors: M. Houdova Megova ¹; J. Drábek ¹; Z. Dwight ²; R. Trojanec ¹; V. Koudelakova ¹; J. Vrbková ¹; O. Kalita ³; S. Mlcochova ¹; M. Rabcanova ¹; M. Hajdúch ¹
Authors‘ workplace: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry Palacky University and University Hospital in Olomouc, Czech republic ¹; Department of Pathology, University of Utah, Salt Lake City, Utah, USA ²; Department of Neurooncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Czech republic ³
Published in: Klin Onkol 2017; 30(5): 361-371
Category: Original Articles
doi: https://doi.org/10.14735/amko2017361

Overview

Východiska:
Mutace isocitrátdehydrogenázy 1 a 2 (IDH1/2) jsou slibným prognostickým biomarkerem gliálních nádorů. Cílem naší studie bylo ověřit prognostický efekt IDH1/2 mutací na skupině pacientů s gliálními nádory z České republiky při použití jednoduché a spolehlivé IDH genotypizace.

Materiál a metody:
U 145 pacientů s gliálními nádory bylo provedeno vyšetření tří nejčastějších IDH mutací IDH1 R132H, IDH1 R132C a IDH2 R172K pomocí kompetitivní polymerazové řetězové reakce (PCR) amplifikace amplikonů s odlišnou teplotou tání (competitive amplification of differentially melting amplicons – CADMA PCR). Dále byla stanovena metylace promotoru O⁶-metylguanine-DNA metyltransferáza (MGMT), počet kopií genů EGFR, p53, RB1, MDM2, CDKN2A a chromozomálních regionů 1p, 19q a 10p. Výsledky byly korelovány s klinickými charakteristikami pacientů.

Výsledky:
IDH mutace byly pozitivně asociovány s MGMT metylací (OR 3,08, 95% CI 1,387–7,282; p = 0,007), 1p/19q kodelecí (OR 8,85, 95% CI 2,367–42,786; p = 0,002) a negativně asociovány s EGFR amplifikací (OR 0,12, 95% CI 0,019–0,437; p = 0,006) a ztrátou 10p (OR 0,09, 95% CI 0,005–0,436; p = 0,019). Celkové přežívání ve skupině IDH-mutovaných glioblastomů bylo 25 měsíců, zatímco u IDH-wild-type glioblastomů pouze 9 měsíců (p = 0,035) a současně se přežívání pacientů s metylovaným vs. nemetylovaným promotorem MGMT významně nelišilo (p = 0,166).

Závěr:
Navzdory tomu, že IDH1/2 mutace jsou úzce asociovány s MGMT metylací u pacientů s gliálními nádory, ve skupině glioblastomů se IDH1/2 mutace jeví jako silnější prognostický marker než MGMT metylace a měly by být biomarkerem první volby pro určení prognózy gliálního nádoru, zvláště při použití genotypizační metody CADMA PCR.

Klíčová slova:
isocitrátdehydrogenáza – polymerázová řetězová reakce – gliom – glioblastom

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Tato práce byla podpořena Ministerstvem zdravotnictví (NT 13581), Technologickou agenturou (TE02000058), Ministerstvem školství, mládeže a tělovýchovy (LM2015089) České republiky. Infrastruktura projektu byla podpořena grantem Národního programu udržitelnosti (NPU LO1304).

Obdrženo:
3. 5. 2017

Přijato:
23. 7. 2017

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