Identification of the Cell Lineage at the Origin of Basal Cell Carcinoma

The document from 2010 reports on a study that investigated the origin of basal cell carcinoma (BCC) in mice. The researchers used genetic mouse models to activate Hedgehog signaling in different skin compartments and found that BCC does not originate from hair follicle bulge stem cells. Instead, BCC arises from long-term resident progenitor cells of the interfollicular epidermis and the upper infundibulum. Clonal analysis showed that 93% of BCCs originated from interfollicular epidermis cells, and the expression of Smoothened (SmoM2) in these cells was sufficient to induce BCC formation. The study suggests that the characteristics of tumor cells may not accurately indicate the cancer-initiating cells and highlights the potential relevance of these findings to human BCC, given the similarities between mouse and human BCC and the likelihood of ultraviolet light affecting interfollicular epidermis cells. Quantitative PCR analysis was used to measure gene expression, and a minimum of 110 pilosebaceous units from three separate mice were analyzed for one group, with a minimum of 125 units from two different mice for other groups, and 1,380 units from two different mice for the ShhCREER/RosaSmoM2 mice. The study aimed to identify the specific cell types within the pilosebaceous unit that give rise to BCC when expressing the SmoM2 mutation.