IDH1 and IDH2 Mutations Test Description: Detection of mutations in ...

IDH1 and IDH2 Mutations
Test Description:
Detection of mutations in the IDH1 and IDH2 genes in brain tumors.
Indication:
Mutations in either isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2)
genes have recently been identified in a large proportion of diffuse astrocytomas (70‐90%),
oligodendrogliomas (69‐94%), oligoastrocytomas (78‐100%), and secondary
glioblastomas (82‐88%)(1‐7). Primary glioblastomas showed low frequency of IDH1/IDH2
mutations (0‐5%). These mutations are not found in non‐neoplastic conditions that can
often mimic gliomas (e.g. radiation changes, viral infections, infarctions, etc.) (7).
Approximately 90% of all mutations occur in codon 132, exon 4 of the IDH1 gene, and less
frequently in codon 172, exon 4 of the IDH2 gene (4). It appears that patients with tumors
harboring IDH1 and IDH2 mutations have better outcome than those with wild‐type IDH
genes (4, 6).
1. Balss J, Meyer J, Mueller W, et al. Analysis of the IDH1 codon 132 mutation in brain
tumors. Acta Neuropathol 2008:116;597‐602.
2. Bleeker FE, Lamba S, Leenstra S, et al. IDH1 mutations at residue p.R132
(IDH1(R132)) occur frequently in high‐grade gliomas but not in other solid tumors.
Hum Mutat 2009:30;7‐11.
3. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human
glioblastoma multiforme. Science 2008:321;1807‐12.
4. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med
2009:360;765‐73.
5. Kang MR, Kim MS, Oh JE, et al. Mutational analysis of IDH1 codon 132 in glioblastomas
and other common cancers. Int J Cancer 2009:125;353‐5.
6. Sanson M, Marie Y, Paris S, et al. Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an
Important Prognostic Biomarker in Gliomas. J Clin Oncol 2009.
7. Horbinski C, Kofler J, Kelly L, Murdoch GH, Nikiforova MN. The diagnostic utility of
IDH1/2 mutation analysis in routine clinical testing of formalin‐fixed paraffinembedded
glioma tissues. J Neuropathol Exp Neurol 2009 (in press).
Methodology:
H&E slides are reviewed by a pathologist to confirm the specimen adequacy and select an
area of tumor for the molecular analysis. Tumor cells are manually microdissected for DNA
isolation. Real time PCR and post‐PCR melting curve analysis is used for detection of
mutations. Positive results are confirmed by sequencing analysis.

Loci Tested:
IDH1 and IDH2
Performed: Mon‐Fri
Reported: Within 5 business days of receipt.
Specimens Required:
1 H&E and 6 blank slides or frozen tissue.
Shipment Must Include:
1 H&E and 6 blank slides of each block or frozen tissue
MAP lab requisition form
Patient’s pathology report