Genomic characterization of metastatic ultra-hypermutated interdigitating dendritic cell sarcoma through rapid research autopsy.

Chen HZ, Bonneville R, Yu L, Wing MR, Reeser JW, Krook MA, Miya J, Samorodnitsky E, Smith A, Martin D, Dao T, Guo Q, Liebner D, Freud AG, Allenby P, Roychowdhury S
Oncotarget 10 277-288 01/08/2019

Abstract

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare cancer of dendritic cell origin that lacks a standardized treatment approach. Here, we performed genomic characterization of metastatic IDCS through whole exome sequencing (WES) of tumor tissues procured from a patient who underwent research autopsy. WES was also performed on a treatment-naïve tumor biopsy sample obtained from prior surgical resection. Our analyses revealed ultra-hypermutation, defined as >100 mutations per megabase, in this patient's cancer, which was further characterized by the presence of three distinct mutational signatures including UV radiation and APOBEC signatures. To characterize clonal heterogeneity, we used the bioinformatics tool Canopy to leverage single nucleotide and copy number variants to catalog six subclones across various metastatic tumors. Truncal alterations, defined as being present in all clonal tumor cell populations, in this patient's cancer include point mutations in

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