A. Dedeilia1, K. Krause1, T. Sharova1, W. Michaud1, D. Liu2, G. Boland1 1Massachusetts General Hospital, Department Of Surgery, Boston, MA, USA 2Dana Farber Cancer Insititute, Department Of Medical Oncology, Boston, MA, USA
Introduction:
Although cutaneous melanoma has been the focus of multiple recent studies, mucosal (MM) and acral (AM) melanoma remain two rare (1-2% and 2-3% of melanomas respectively) and understudied forms of the same cell origin. They are more prevalent among women and non-Caucasian populations and have a higher rate of metastasis at presentation and worse prognosis and response to treatment. Thus, it becomes essential to investigate the biology, microenvironmental interactions and potential therapeutic candidates of MM and AM, to bridge the current evidence gap.
Methods:
A biobank of more than 30 MM and 30 AM were retrieved from a large cohort of melanoma patients. The tumor specimens are being studied via bulk sequencing, including targeted sequencing, whole exome sequencing (WES) and RNA sequencing (RNAseq) to identify somatic mutations and transcriptomic features of cell populations involved in tumorigenesis and responsiveness to therapy. Also, single-cell RNA sequencing (scRNAseq) performed on a subset of patients provides transcriptome information on individual cells and assists in the documentation of the expression of specific protein targets.
Results:
Pilot data demonstrates that MM cells express SOX10, a potential therapeutic target shared with cutaneous melanoma (CM). Furthermore, data shows that compared to CM, MM tumors lack memory/effector T cells and IFN-activated myeloid cells, which have been associated with successful checkpoint immunotherapy in melanoma, while they had high numbers of gamma/delta T cells, cytotoxic CD8 T cells, and macrophage/monocytes thought to create an immunosuppressive microenvironment. Ongoing efforts are focused on expansion and validation of the preliminary findings.
Conclusion:
This work provides a highly needed map of these rare cancers (AM and MM). Bulk sequencing sheds light to the intercellular microenvironmental interactions, and single cell RNA sequencing provides valuable information on the expression of candidate targets that will drive further research for the respective novel therapeutic targets for AM and MM.