Cancers that arise in epithelial tissue, such as lung, breast, colon, prostate, and skin, account for approximately 90 percent of all human malignancies. These carcinomas affect over 30 million individuals worldwide and are the second leading cause of death in the United States. Work in our lab utilizes high-throughput sequencing approaches to gain a deeper understanding of the diversity, function, and clinical significance of the somatic alterations present in skin cancer genomes. Sequencing of tumors and matched normal tissue has the potential to highlight previously unexplored disease mechanisms, identify prognostic markers, and even transform clinical practice with effective targeted therapies. Insight gained from studying skin cancer may inform our understanding of other epithelial malignancies as well.
We were the first to identify hotspot mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma (SCC) that trigger aneuploidy and accelerate tumorigenesis [Nature Genetics (2014)].
We also helped demonstrate KNSTRN mutations in basal cell carcinoma (BCC) [Journal of Investigative Dermatology (2015)].
Discovery of the mechanisms that underlie KNSTRN’s pro-tumorigenic effects along with identifying new cancer genes is a major focus of our lab. Work by our group has also focused on cutaneous T-cell lymphoma (CTCL), a non-Hodgkin lymphoma of clonally-derived, skin-homing T-cells that includes mycosis fungoides and Sézary syndrome.
We were the first to define the Sézary cell transcriptome by RNA sequencing [Blood (2012)] and helped establish recurrent alterations in TNFR2 in CTCL that regulate T-cell proliferation and survival using exome sequencing [Nature Genetics (2015)]. These efforts also identified long noncoding RNAs (lncRNAs) that are dysregulated in CTCL with potential roles in this malignancy.