IDH1 Mutation Testing

Performing Lab:

UCSF Clinical Cancer Genomics Lab

CPT Code:

81403, 88381

Specimen Type: Formalin-fixed, paraffin-embedded tissue. Tissue block or unstained slides. If sending unstained slides, we require five (5) 10-micron tissue sections on uncharged glass slides. One adjacent H&E stained slide should be included. Cytology smears may also be used for testing if there is sufficient tumor present. Contact the laboratory at 415.502.3252 or [email protected] if testing on a cytology smear is desired.
Methodology: Sanger sequencing
Turnaround Time: 7-14 days

TEST INDICATIONS:

IDH mutations are present in approximately 80% of grade II-III infiltrating gliomas and secondary glioblastomas, which arise from lower grade tumors. Primary glioblastomas, which present as high grade tumors and carry a worse prognosis, rarely harbor IDH mutations. As such, the presence of IDH mutation suggests that a glioblastoma is secondary. IDH mutation is associated with better outcomes in high-grade glioma, with a median overall survival of 31 months for patients with an IDH1-mutant glioblastoma and 15 months for patients with wild-type IDH1. Similarly, the absence of IDH mutation in low-grade glioma has been found to be predictive of a briefer latency to malignant transformation and a shorter overall survival.

IDH mutations are also present in a subset of acute myeloid leukemia. The prognostic significance of IDH mutation is context dependent. In patients with normal karyotype and an NPM1 mutation, IDH mutations are associated with favorable prognosis in AML.

HOW THE TEST WORKS:

For tissue specimens, a histologic section of formalin-fixed, paraffin-embedded tissue is examined by a pathologist to identify an area of tissue with sufficient tumor for detection (>=50% tumor if possible). DNA is extracted from tumor areas on adjacent unstained slides. For fresh specimens, genomic DNA is extracted from a blood or bone marrow specimen, collected in EDTA. The exons 4 and 5 of the IDH1 gene are captured and sequenced by next generation sequencing.

LIMITATIONS OF THE TEST:

Results of this test should be correlated with the patient’s other clinical and laboratory information. This assay only detects mutations in codons 96 through 138 of the IDH1 gene.

This test was validated by the UCSF Clinical Cancer Genomics Laboratory to confirm performance characteristics, in compliance with current guidelines for clinical implementation.

SPECIMEN REQUIREMENTS FOR A SUCCESSFUL TEST:

In general, the tumor should be a minimum of 0.4 cm in size. Blocks selected for IDH1 Mutation Testing must contain tumor tissue. Areas of tumor must contain at least 50% tumor cells. The lab can remove adjacent non-tumor tissue, so the entire slide does not need 50% tumor cells, just the area with tumor. Contact the laboratory at 415.502.3252 or [email protected] if the specimen suitability is uncertain. Label slides with pathology case number and block identification.

Specimen rejection criteria include: All required slides not included. Insufficient tumor tissue present on slide as determined by pathologist. Outside slides not labeled or not accompanied by printed copy of test order.

HOW TO ORDER THE TEST:

UCSF Clinicians — this test can be ordered through APeX
Outside Physicians — this test can be ordered using the CCGL Requisition Form

For all specimens, an interpretation of this test by a laboratory physician will automatically be performed and billed for separately.