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May 12, 2021

Two Trajectories to Melanoma on the Hands and Feet

Author Affiliations
  • 1University of California, San Francisco
JAMA Dermatol. Published online May 12, 2021. doi:10.1001/jamadermatol.2021.0792

Acral melanoma is a subtype of melanoma that occurs on the glabrous (non–hair-bearing) skin of the hands and feet. The incidence of acral melanoma is similar across people of different races and ethnicities. At the genetic level, acral melanomas have diverse mutations known to activate the mitogen-activated protein kinase (MAPK) pathway.1,2 Their overall point mutation burdens are relatively low, but they are riddled with complex copy number alterations, recently termed tyfonas.3 Tyfonas are “typhoons” of high-junction copy number events and fold-back inversions with hypermutated DNA near the junctional endpoints, which have only been observed in acral melanomas and dedifferentiated liposarcomas.3 Tyfonas can be present in precancerous cells up to 3 mm beyond the clinical or histological boundary of acral melanomas, suggesting that these alterations arise early during tumorigenesis and give rise to fields of poised cells that can eventually progress into melanoma.4

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