BACKGROUND AND OBJECTIVE: It has been shown that somatic missense mutations in codon 132 of the NADP+ dependent isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors including highly malignant glioblastoma (GBM). The aim of this study was to evaluate a PCR-restriction fragment length polymorphism (RFLP)-based method for missense mutation detection and to estimate the prognostic value of the two most frequent IDH1 codon 132 mutations, R132H and R132C, in patients with newly diagnosed GBM treated with radiation combined with temozolomide. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue. The PCR-RFLP method was adapted to IDH1 codon 132 mutation screening. The mutation status was determined in a group of 58 patients. RESULTS: We found R132H mutations in 14% of patients. No R132C mutation was found in this study. Median follow-up for living patients was 31 (range 17-51) months. Median progression-free survival in the group of patients with IDH1 mutation was 29 months compared with 10 months in the IDH1 wild-type group (p = 0.004; hazard ratio [HR] 3.09, 95% CI 1.25, 4.78). Median overall survival in the group with IDH1 mutation has not been reached, whereas in the group with wild-type IDH1 it was 19.5 months (p < 0.001; HR 4.76, 95% CI 1.22, 6.30). Three-year overall survival was 60% in the group with IDH1 mutation while in the wild-type IDH1 group it dropped to 29%. IDH1 mutations significantly correlated with younger age (p = 0.02). CONCLUSIONS: Our results indicate that the IDH1 R132H mutation is a powerful prognostic marker in GBM treated with chemoradiation. The PCR-RFLP method allows for a fast, inexpensive, and sensitive mutation screening.
BACKGROUND AND OBJECTIVE: It has been shown that somatic missense mutations in codon 132 of the NADP+ dependent isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors including highly malignant glioblastoma (GBM). The aim of this study was to evaluate a PCR-restriction fragment length polymorphism (RFLP)-based method for missense mutation detection and to estimate the prognostic value of the two most frequent IDH1 codon 132 mutations, R132H and R132C, in patients with newly diagnosed GBM treated with radiation combined with temozolomide. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue. The PCR-RFLP method was adapted to IDH1 codon 132 mutation screening. The mutation status was determined in a group of 58 patients. RESULTS: We found R132H mutations in 14% of patients. No R132C mutation was found in this study. Median follow-up for living patients was 31 (range 17-51) months. Median progression-free survival in the group of patients with IDH1 mutation was 29 months compared with 10 months in the IDH1 wild-type group (p = 0.004; hazard ratio [HR] 3.09, 95% CI 1.25, 4.78). Median overall survival in the group with IDH1 mutation has not been reached, whereas in the group with wild-type IDH1 it was 19.5 months (p < 0.001; HR 4.76, 95% CI 1.22, 6.30). Three-year overall survival was 60% in the group with IDH1 mutation while in the wild-type IDH1 group it dropped to 29%. IDH1 mutations significantly correlated with younger age (p = 0.02). CONCLUSIONS: Our results indicate that the IDH1R132H mutation is a powerful prognostic marker in GBM treated with chemoradiation. The PCR-RFLP method allows for a fast, inexpensive, and sensitive mutation screening.
Authors: Lenny Dang; David W White; Stefan Gross; Bryson D Bennett; Mark A Bittinger; Edward M Driggers; Valeria R Fantin; Hyun Gyung Jang; Shengfang Jin; Marie C Keenan; Kevin M Marks; Robert M Prins; Patrick S Ward; Katharine E Yen; Linda M Liau; Joshua D Rabinowitz; Lewis C Cantley; Craig B Thompson; Matthew G Vander Heiden; Shinsan M Su Journal: Nature Date: 2009-12-10 Impact factor: 49.962
Authors: Mi Ran Kang; Min Sung Kim; Ji Eun Oh; Yoo Ri Kim; Sang Yong Song; Seong Il Seo; Ji Youl Lee; Nam Jin Yoo; Sug Hyung Lee Journal: Int J Cancer Date: 2009-07-15 Impact factor: 7.396
Authors: D Williams Parsons; Siân Jones; Xiaosong Zhang; Jimmy Cheng-Ho Lin; Rebecca J Leary; Philipp Angenendt; Parminder Mankoo; Hannah Carter; I-Mei Siu; Gary L Gallia; Alessandro Olivi; Roger McLendon; B Ahmed Rasheed; Stephen Keir; Tatiana Nikolskaya; Yuri Nikolsky; Dana A Busam; Hanna Tekleab; Luis A Diaz; James Hartigan; Doug R Smith; Robert L Strausberg; Suely Kazue Nagahashi Marie; Sueli Mieko Oba Shinjo; Hai Yan; Gregory J Riggins; Darell D Bigner; Rachel Karchin; Nick Papadopoulos; Giovanni Parmigiani; Bert Vogelstein; Victor E Velculescu; Kenneth W Kinzler Journal: Science Date: 2008-09-04 Impact factor: 47.728
Authors: Michael Weller; Jörg Felsberg; Christian Hartmann; Hilmar Berger; Joachim P Steinbach; Johannes Schramm; Manfred Westphal; Gabriele Schackert; Matthias Simon; Jörg C Tonn; Oliver Heese; Dietmar Krex; Guido Nikkhah; Torsten Pietsch; Otmar Wiestler; Guido Reifenberger; Andreas von Deimling; Markus Loeffler Journal: J Clin Oncol Date: 2009-10-05 Impact factor: 44.544