Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms

Abstract

Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.

Basal cell carcinoma: biology, morphology and clinical implications

“…Roughly onequarter of cases occur on the nose, the most frequently involved site. [2][3][4][5][6] Less prevalent overall in more darkly pigmented races, the histologic types of BCC seen in Africans and Hispanics have a similar histomorphology. 89 Other Risk Factors for Sporadic BCC…”

“…[2][3][4] After a rise in incidence of roughly 20% between 1971 and 1977, 5 by 1998 roughly one million new cases were being diagnosed annually in the United States. 6 In consequence of its high incidence, BCC, although eminently curable when the diagnosis is made promptly and the lesion treated in its early phase, constitutes an enormous financial burden on the health care system.…”

Analysis of the vitamin D system in basal cell carcinomas (BCCs)

“…18 The hedgehog signaling pathway has been identified to be crucial to the development of basal cell carcinomas. 20,21 However, the biological mechanisms underlying the unique characteristics of BCC tumor growth are still completely unknown. 22 There are two principal enzymes involved in the formation of circulating 1a,25(OH) 2 D 3 from vitamin D, the hepatic microsomal or mitochondrial vitamin D-25-hydroxylase (25-OHase) and the renal mitochondrial enzyme 1a-hydroxylase (1a-OHase) for vitamin D and 25(OH)D 3 , respectively.…”

Prevalência do herpes-vírus humano tipo 1 em neoplasias cutâneas epiteliais malignas

“…Além disso, existem alguns genes, como o que codifica a proteína p53 e gene patched, marcadores importantes da indução de neoplasia pela radiação ultravioleta, que podem sofrer mutações. 24 Diante de amostra representativa, a fim de comparação, foi necessário utilizar parâmetro semelhante entre os grupos de estudo e controle; no caso, as amostras de pele normal. Dessa forma, pôde-se demonstrar neste estudo a presença significativa do HHV1 na pele sã de indivíduos não portadores de neoplasias cutâneas, quando comparada à pele sã daqueles com neoplasias.…”