A 77-year-old man has a lesion on the right side of his face that has enlarged slowly over the past 5 years. On examination, the 3-cm lesion has irregular borders, irregular brown to black pigmentation, and a central 2-mm raised blue-black nodule. The lesion is resected and microscopically shows radial growth of large round malignant cells, some isolated and others in nests in the epidermis and superficial papillary dermis. The cells have prominent red nucleoli and dust-like cytoplasmic pigment. Which of the following mutated genes is most likely to be present in the skin lesion of this man?
He has lentigo malignant melanoma, which exhibits an indolent radial growth phase for many years before reaching an accelerated nodular vertical growth phase. Most of these lesions arise on the skin of the head and neck of elderly persons. Activating BRAF mutations are downstream from RAS mutations and are present in the majority of malignant melanomas. ATM gene mutations underlie ataxia-telangiectasia, in which there are dilated subepidermal blood vessels forming lesions called telangiectasias. NF1 mutations are associated with the appearance of many dermal neurofibromas. TYR mutations are seen in association with albinism; TYR encodes the enzyme tyrosinase that is part of the initial pathway of melanin production by melanocytes. Mutations in the XP family of genes are seen with xeroderma pigmentosum, in which defects in DNA excision repair predispose to skin cancers (basal cell carcinoma, squamous cell carcinoma, malignant melanoma) starting in childhood from exposure to ultraviolet light.
ATM
BRAF
NF1
TYR
Skin