MITF

Overview

MITF (Microphthalmia-Associated Transcription Factor) is the master transcriptional regulator of melanocyte identity, differentiation, and survival. It controls expression of key pigmentation genes (TYRP1, DCT, PMEL, MLANA) and melanocyte-lineage markers. MITF amplification and altered expression are drivers in melanoma; it also serves as a canonical lineage-confirmation marker distinguishing melanocytes from other skin cell types.

Alterations observed in the corpus

  • Used as a melanocyte lineage-confirmation marker in a normal human skin atlas study profiling 297 single melanocytes from 31 donors with matched DNA/RNA sequencing and Xenium spatial validation; co-expressed with PMEL, TYRP1, and MLANA to confirm melanocyte identity in clonal expansion and Xenium spatial data. No somatic MITF alterations are reported as study endpoints. PMID:39975212
  • MITF amplification was identified as a genomic feature in cancer cell lines profiled in the CCLE pharmacogenomic study across 947 lines and 24 drugs PMID:22460905
  • MITF identified as a significantly mutated gene in melanoma WGS analysis of 25 tumors PMID:22622578
  • Listed among recurrently altered genes in melanoma WES of 121 tumors (Broad cohort); associated with transcriptional regulation in melanocytes PMID:22817889
  • Relapse-associated focal amplification in resistant melanoma tumors; overexpression confers pan-MAPK-inhibitor cross-resistance (30–80-fold) in WM266.4/SKMEL19/UACC62 cell lines; represents a transcriptional-effector resistance mechanism PMID:24265153
  • ACTG1-MITF fusion identified in pRCC (sample 159T); activates HIF1A, MET, and APEX1; greater protein stability and transforming activity than wild-type MITF; defines ‘MiTF-high’ subtype alongside TFE3/TFEB fusions and amplifications PMID:25401301
  • MITF focal amplifications in BRAF-mutant cutaneous melanoma subtype (TCGA 333-sample cohort); recurrent fusions identified (MITF-FOXP1, CADM2-MITF, FRMD4B-MITF); defines a low-expression transcriptomic subclass PMID:26091043
  • Notably absent from the top 421 differentially expressed genes used for expression clustering in acral lentiginous melanoma (ALM), in contrast to its key role in cutaneous melanoma; this absence distinguishes ALM’s transcriptional landscape from CM PMID:28373299
  • Non-DNA-repair presumed pathogenic germline mutation (PPGM) identified in 5 of 500 metastatic cancer patients (8%), enriched vs. ExAC controls; implicated as a germline cancer-predisposition gene across cancer types in MET500 cohort PMID:28783718

Cancer types (linked)

  • MEL (melanoma): MITF is a well-established melanoma lineage oncogene (amplified in ~10–20% of melanomas) but no MITF amplification or mutation data are primary endpoints in the citing paper. The FFPE Xenium specimen was from non-lesional adjacent skin of a melanoma patient. PMID:39975212

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No MITF-directed therapeutic intervention reported in the corpus for this paper.

Open questions

  • Whether differential MITF expression levels between HighMut and LowMut melanocyte subpopulations underlies their distinct transcriptional programs is not addressed. PMID:39975212

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22460905

This page was processed by crosslinker on 2026-05-14. - PMID:22622578

This page was processed by crosslinker on 2026-05-14. - PMID:22817889

This page was processed by crosslinker on 2026-05-14. - PMID:24265153

This page was processed by crosslinker on 2026-05-14. - PMID:25401301

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:28373299

This page was processed by wiki-cli on 2026-05-14. - PMID:28783718

This page was processed by wiki-cli on 2026-05-15.