DAAM2

Overview

DAAM2 (Dishevelled Associated Activator of Morphogenesis 2) is a formin-family protein involved in actin polymerization and WNT signaling. In single-cell atlas profiling of normal human skin, DAAM2 is expressed by the low-UV-mutation-burden (LowMut) melanocyte subpopulation, which has a neural-crest stem-cell transcriptional signature.

Alterations observed in the corpus

  • DAAM2 was identified as a LowMut melanocyte transcriptomic marker upregulated in the low-UV-mutation-burden, stem-like melanocyte subpopulation (versus the HighMut UV-damaged subpopulation) in a joint DNA/RNA single-cell profiling study of 297 melanocytes from 58 skin biopsies across 31 donors. LowMut cells overexpressing DAAM2, FBN1, VCAN, SEMA3C, and other neural-crest genes are spatially enriched in hair follicles in the 10X Xenium spatial transcriptomic validation PMID:39975212.

Cancer types (linked)

  • Normal skin / MEL adjacent — DAAM2 defines the LowMut neural-crest-like melanocyte stem cell compartment; no somatic mutations in DAAM2 were reported; study was a normal-tissue cell atlas PMID:39975212.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Not directly targeted therapeutically; identified as a stem-cell niche marker relevant to melanoma origin biology.

Open questions

  • Whether DAAM2-high melanocyte stem cells serve as the melanoma cell-of-origin is an open question not tested in this study.

Sources

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