Frequent mutations in the MITF pathway in melanoma

Julia C. Cronin, John Wunderlich, Stacie K. Loftus, Todd D. Prickett, Xiaomu Wei, Katie Ridd, Swapna Vemula, Allison S. Burrell, Neena S. Agrawal, Jimmy C. Lin, Carolyn E. Banister, Phillip Buckhaults, Steven A. Rosenberg, Boris C. Bastian, William J. Pavan, Yardena Samuels

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Microphthalmia-associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF is somatically mutated in melanoma, we compared the sequence of MITF from primary and metastatic lesions to patient-matched normal DNA. In the 50 metastatic melanoma tumor lines analysed, we discovered four samples that had genomic amplifications of MITF and four that had MITF mutations in the regions encoding the transactivation, DNA binding or basic, helix-loop-helix domains. Sequence analysis for SOX10, a transcription factor, which both acts upstream of MITF and synergizes with MITF, identified an additional three samples with frameshift or nonsense mutations. Microphthalmia-associated transcription factor and SOX10 were found to be mutated in a mutually exclusive fashion, possibly suggesting disruption in a common genetic pathway. Taken together we found that over 20% of the metastatic melanoma cases had alterations in the MITF pathway. We show that the MITF pathway is also altered in primary melanomas: 2/26 demonstrated mutations in MITF and 6/55 demonstrated mutations in SOX10. Our findings suggest that altered MITF function during melanomagenesis can be achieved by MITF amplification, MITF single base substitutions or by mutation of its regulator SOX10.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalPigment Cell and Melanoma Research
Issue number4
StatePublished - Aug 2009
Externally publishedYes


  • 5-7 MITF
  • Melanoma
  • Mutations
  • P21
  • SOX10
  • Sequencing

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology


Dive into the research topics of 'Frequent mutations in the MITF pathway in melanoma'. Together they form a unique fingerprint.

Cite this