Interview with Dr. Sameek Roychowdhury & Dr. Hui Zi Chen from Ohio State University

The cover for issue 3 of Oncotarget features images of a research autopsy to characterize clonal heterogeneity in a rare hypermutated cancer, by Chen, et al.

The research team's analyses revealed ultra-hypermutation, defined as >100 mutations per megabase, in this patients cancer, which was further characterized by the presence of three distinct mutational signatures including UV radiation and APOBEC signatures.

Truncal alterations, defined as being present in all clonal tumor cell populations, in this patients cancer include point mutations in TP53 and CDKN2A and amplifications of c-KIT and APOBEC3A-H, which are likely driver mutations.

Dr. Sameek Roychowdhury from the Department of Internal Medicine, Division of Medical Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA said, "Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy of dendritic cell origin with approximately 100 cases reported to date"

Localized IDCS constitutes 47% of cases and manifests as painless lymphadenopathy, most commonly involving the cervical and axillary nodes.

Isolated extra-nodal disease occurs in 25% of cases, involving the liver, lung, spleen, bone marrow and gastrointestinal tract.

Distant metastases occur in 39% of cases and most frequently involved lymph nodes, lung, liver and bone marrow.

Here they performed whole exome sequencing of multiple tumors obtained through rapid research autopsy of a patient with metastatic IDCS. In August 2016, the patient underwent modified radical right neck dissection and partial submandibular gland excision with one level I lymph node demonstrating complete tumor involvement and suspicious for extranodal extension; remaining lymph nodes from levels II, III and IV were negative for tumor infiltration.

In the future, it will be important to study additional patients with this and other rare cancers with hypermutation.

The Roychowdhury research team concluded, "Finally, the broader clinical implication of our results is that although patients with hypermutated cancer, originating from either somatic or germline genomic aberrations, are more likely to benefit from checkpoint inhibition, research is still needed to stratify these patients to maximize therapeutic efficacy and identify the different genetic determinants of primary or acquired resistance to immunotherapy."

Full text - https://www.oncotarget.com/article/26352/text/

Correspondence to - Sameek Roychowdhury email: [email protected]

Keywords - tumor heterogeneity, research autopsy, hypermutation