MAP2K1 mutation analysis is performed by next-generation sequencing of all coding exons of the MAP2K1 gene (formerly named MEK1).
Mitogen-activated protein kinase kinase 1 (MAP2K1) encodes a mitogen-activated protein kinase (MEK1) that activates MAPK signal transduction. MAP2K1 mutations have been described in several cancers including histiocytic neoplasms, hairy cell leukemia, melanoma, and lung cancer. MEK1 mutations may enhance or suppress MEK1 activity depending on the precise variant. Somatic MAP2K1 mutations are found in 33-50% of Langerhans cell histiocytosis (LCH) cases lacking BRAF mutation and are mutually exclusive of BRAF mutation. Mutations in MAP2K1 are also found in half of hairy cell leukemia-variant (HCL-V) cases, but are less frequent in classic HCL cases which have a BRAF mutation instead. The presence of MAP2K1 mutation may also be useful in differentiating high and low-risk LCH. Patients with histiocytic neoplasms, including LCH, with MEK1 mutations have been shown to benefit from MEK1/2 inhibitor therapy. MAP2K1 mutations have been demonstrated to confer resistance to BRAF inhibitors in some cancers.
- Peripheral blood: 5 mL in EDTA tube.
- Bone marrow: 2 mL in EDTA tube.
- FFPE tissue: Paraffin block is preferred. Alternatively, send 1 H&E slide plus 5-10 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative. Do not use zinc fixatives.
Use cold pack for transport, making sure cold pack is not in direct contact with specimen.
- Jindal GA, Goyal Y, Humphreys JM, et al. How activating mutations affect MEK1 regulation and function. J Biol Chem. 2017;292(46):18814-18820.
- Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007-3015.
- Troussard X, Cornet E. Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment. Am J Hematol. 2017;92(12):1382-1390.
- Papapanagiotou M, Griewank KG, Hillen U, et al. Trametinib-Induced Remission of an MEK1-Mutated Langerhans Cell Histiocytosis. JCO Precis Oncol. 2017;1:1-5.
- Gounder MM, Solit DB, Tap WD. Trametinib in histiocytic sarcoma with an activating MAP2K1 (MEK1) mutation. N Engl J Med. 2018;378(20):1945-1947.