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Genomic Characterization and Molecular Taxonomy of Sarcomatoid Variant Prostate Cancer

ASCO Genitourinary Cancers Symposium 2021 Presentation
Authors Mary Duong, Alex Barrett, Jeff Schaeffer, Tim Taxter, and Mitchell E. Gross

Background: Sarcomatoid carcinoma is a rare and aggressive histologic variant pattern of prostate cancer with morphologic features associated with both mesenchymal and epithelial tissue elements. While sarcomatoid cancer can be found concurrently with adenocarcinoma in untreated specimens, it is most often encountered in post-treatment biopsies. Limited data is available to categorize genomic alterations in sarcomatoid prostate cancer or to genetically define any potential relationship between sarcomtaoid and adenocarcinoma patterns from the same patient.

Methods: Clinical characteristics, histology, and genomic alterations for 5 cases of sarcomatoid prostate cancer and 2193 cases with adenocarcinoma are presented. All cases were analyzed for genomic alterations against a custom panel via Tempus xT tissue biopsy assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth and whole transcriptome RNA sequencing) for germline and/or somatic mutations. The xT assay detects single nucleotide variants, specific insertion/deletions, amplifications and gene fusions, as well as TMB and MSI status.

Results: Patterns of genomic alterations in sarcomatoid cancer are tabulated and compared with adenocarcinoma. Of note, BRCA2 alterations were found in 2 of 5 sarcomatoid cases including 1 example of BRCA2 loss and 1 variant of undetermined significance (p.K2316R). Sequential analysis of samples from the subject with BRCA2 loss demonstrates genomic alterations that are shared across multiple samples despite different histologic patterns and following 14 months of treatment with GnRH antagonist and abiraterone (Table).

Conclusions: Sarcomatoid prostate cancer shares many genomic alterations with that found in adenocarcinoma. Genomic characterization of this variant form of prostate cancer may reveal clinically actionable genetic changes.