Hematological Malignancies • Solid Tumors IDH1 and IDH2 Mutation Analysis

Mutations in isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have been found in 70% of grade II-IV gliomas and in approximately 15% of acute myeloid leukemias (AML).   These mutations alter arginine 132 (R132) in IDH1, and either R140 or R172 in IDH2.  In AML, presence of these mutations confers an adverse prognosis and will likely be the target for drugs in development.

DNA is purified and extracted from leukemia and/or solid tumor cells (with macro-dissection if required).  Screening for mutations is then performed by one of two methods:  PCR amplification of IDH targets followed by bidirectional Sanger sequencing of each exon; or real-time PCR with high resolution melting curve analysis (HRM) followed by reflex sequencing to confirm positive HRM screens.

• Formalin-fixed paraffin-embedded tumor block or FFPE slides: 
  • If sending slides, please include H&E stained slide cut from same block
  • Preferred slice thickness is 4-5 microns on  positively charged slides. 
  • Please submit 10 slides (15 for small biopsies).  Store at room temperature.
  • Due to DNA damage, decalcified specimens are not recommended.
• Blood or bone marrow: 
  • 2-10 mL - yellow (ACD) or purple (EDTA) tube (unspun).
  • Bone marrow aspirates or cores are acceptable if received in the lab within 24 hours (room temperature) or 4 days (refrigerated; never frozen).
  • Frozen cell pellets of bone marrow-derived leukocytes (without red blood cells) are also acceptable.

Contact Client Services for shipping materials and procedures at (855) 535-1522.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Mon - Sat

7 - 10 days

• Package and ship specimen to remain cool during transit, but not frozen, unless shipping frozen pellets.
• Ship via overnight express, using the FedEx priority overnight label provided.
• Contact Client Services for shipping kits and instructions at (855) 535-1522.

1. Marcucci G, Maharry K, Wu YZ, et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.  J Clin Oncol. 2010;28:2348-55.
2. Nobusawa S, Watanabe T, Kleihues P, Ohgaki H. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009 Oct 1;15(19):6002-7.
3. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-733.
4. Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN. Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol. 2009 Dec;68(12):1319-25.
5. Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Smitt PA, Dinjens WN, van den Bent MJ. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology. 2009 Nov 24;73(21):1792-5.