26086 Isocitrate Dehydrogenase 1 and 2 (IDH1/IDH2) Mutation Analysis, Tumor (IDH12)

Slide review IDH1 and IDH2 Mutation Analysis

Tissue Block: Submit a formalin-fixed, paraffin-embedded tissue block

Slides: Submit 1 slide stained with hematoxylin and eosin and 10 unstained slides (nonbaked, charged slides preferred) with 5-micron thick sections of the tumor tissue.

Cytology Slides: Submit 1-2 slides stained and coverslipped with at least 5,000 total nucleated cells. Cytology slides will not be returned.

This test cannot differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk.

DNA variants of uncertain significance may be identified.

A negative (wild-type) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay.

Point mutations and small insertion/deletion mutations will be detected within targeted regions of the IDH1, and IDH2 genes only. This test does not detect structural variants, genomic copy number changes, or large single or multiexon deletions or duplications in the IDH1 and IDH2 genes.

Rare polymorphisms may be present that could lead to false-negative or false-positive results. Test results should be interpreted in the context of clinical findings, tumor sampling and other laboratory data. If results obtained do not match other clinical or laboratory findings, please contact the laboratory for updated interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

Reliable results are dependent on adequate specimen collection and processing. This test has been validated on cytology slides and formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.

IDH1 and IDH2 (IDH) genes encode dehydrogenase enzymes that are involved in cellular glucose metabolism and oxidative damage control. IDH mutations, primarily involving codons R132 in IDH1 and R172 in IDH2, result in reduction of the enzyme physiological activity and gain of a neomorphic ability to generate oncometabolite R(-)-2-hydroxyglutarate, which contribute to tumorigenesis by altering numerous cellular responses, including genome-wide epigenetic changes that characterize the glioma CpG island methylator phenotype (G-CIMP). IDH mutations seem to be an early event in gliomagenesis and have been identified in over 70% of lower-grade (grades II/III) diffuse gliomas and secondary glioblastoma. These mutations are rarely seen in other central nervous system tumors and are not seen in reactive non-neoplastic processes, and define a group of lower and high-grade diffuse gliomas associated with a more favorable prognosis. Assessment of IDH mutation status in central nervous system tumors may assist in tumor classification and provide prognostically relevant information for subgroups of patients with diffuse gliomas.

IDH1 and IDH2 gene mutations are also observed in a variety of non-CNS tumor types. Assessment of IDH mutation status may assist in the differential diagnosis of chondroid bone tumors and provide prognostically relevant information in other contexts, such as in the setting of acute myeloid leukemia (AML).