Microphthalmia-associated transcription factor (MITF) – from Waardenburg syndrome genetics to melanoma therapy

Ivan Šamija, Josip Lukač, Zvonko Kusić


Microphthalmia-associated transcription factor (MITF) wasfirst discovered as protein coded by gene whose mutationsare associated with Waardenburg syndrome. Later, MITF wasshown to be key transcription factor regulating melanogenesis.Further studies have shown that in addition to regulatingmelanogenesis MITF also plays central role in regulationof melanocyte development and survival. MITF gene is amplifiedin a proportion of melanomas and ectopic MITF expressioncan transform melanocytes so MITF can functionas melanoma “lineage survival” oncogene. Different studieshave further revealed MITF’s important but complex role intumorigenesis and progression of melanoma. As expectedfrom its important role in melanocytes and melanoma MITFis intricately regulated on all the levels from transcription topost-translational modifications. Although complex mechanismsof MITF functioning are still being revealed, MITFalready has a valuable role in managing melanoma patients.Immunohistochemical analysis of MITF has shown both diagnosticand prognostic value in patients with melanoma.MITF is also a valuable specific marker for detection of circulatingmelanoma cells by reverse-transcription – polymerasechain reaction. MITF has recently been investigated as a potentialtarget for melanoma therapy.


Microphthalmia-associated transcription factor; Melanoma; Melanocytes; Biological tumor markers; Waardenburg’s syndrome

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