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Wednesday, October 18, 2017
2:00 PM - 3:00 PM
CNLS Conference Room (TA-3, Bldg 1690)

Postdoc Seminar

Genomic characterization of basal cell carcinoma of the skin

Ximena Bonilla
University of Geneva Medical

Basal cell carcinoma of the skin (BCC) is the most common malignant neoplasm in humans and it is known to be primarily driven by aberrant activation of the Sonic Hedgehog (Hh) pathway. Because BCC displays extensive variation in phenotype and response to treatment, the possibility of additional signaling pathways and genes involved in its development and progression were worth investigating. The genomic profiling of a large collection of BCCs revealed the highest mutation rate observed in cancer to date (65 Mutations/Mb), with strong prevalence of UV-light signature mutations. As expected, 85% of BCCs harbored mutations in genes of the Hh pathway such as PTCH1 (73%), SMO (20%), and SUFU (8%), as well as in the well-known cancer gene TP53 (61%). Interestingly though, 85% of BCCs also harbored additional driver mutations in other cancer-related genes, such as MYCN (30%), PTPN14 (23%), and LATS1 (8%). Functional analysis of some of these mutations hinted at their role in the upregulation of the Hippo-YAP pathway, as well as in the activation of MYCN target genes. These findings suggest a more complex genetic network of cancer genes than previously anticipated in BCC, providing an expanded molecular understanding of this type of skin cancer.

Host: Boian Alexandrov