Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers.
Missense somatic mutations in IDH1 gene affecting codon 132 have recently been reported in glioblastoma multiforme (GBM) and other gliomas. The recurrent nature of the IDH1 mutations in the same amino acid strongly suggests that the mutations may play important roles in the pathogenesis of glial tumors. The aim of this study was to see whether the IDH1 codon 132 mutations occur in other human cancers besides glial tumors. We also attempted to confirm the occurrence of the IDH1 mutations in GBM of Korean patients. We have analyzed 1,186 cancer tissues from various origins, including carcinomas from breast, colon, lung, stomach, esophagus, liver, prostate, urinary bladder, ovary, uterine cervix, skin and kidney, and malignant mesotheliomas, primary GBM, malignant meningiomas, multiple myelomas and acute leukemias by single-strand conformation polymorphism analysis. We found four IDH1 codon 132 mutations in the GBM (4/25; 16.0%), two in the prostate carcinomas (2/75; 2.7%) and one in the B-acute lymphoblastic leukemias (B-ALL) (1/60; 1.7%), but none in other cancers. The IDH1 mutations consisted of five p.R132H and two p.R132C mutations. The data indicate that IDH1 codon 132 mutations occur not only in GBM, but also in prostate cancers and B-ALL. This study suggests that despite the infrequent incidence of the IDH1 mutations in prostate cancers and B-ALL, mutated IDH1 could be therapeutically targeted in these cancers and in glial tumors with the IDH1 mutations.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Mi Ran
MR
Kang
Min Sung
MS
Kim
Ji Eun
JE
Oh
Yoo Ri
YR
Kim
Sang Yong
SY
Song
Seong Il
SI
Seo
Ji Youl
JY
Lee
Nam Jin
NJ
Yoo
Sug Hyung
SH
Lee
D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D003062:Codon; D017931:DNA Primers; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D020125:Mutation, Missense
D003062:Codon; D017931:DNA Primers; D007521:Isocitrate Dehydrogenase