Michael C. Haffner, MD, PhD, explains the genomic differences between prostate adenocarcinoma of the prostate and prostatic basal cell carcinoma, an extremely rare disease.
Michael C. Haffner, MD, PhD, assistant professor in the Human Biology Division and an assistant professor in the Clinical Research Division at Fred Hutchinson Cancer Center, and colleagues conducted a study exploring potential driver mutations in basal cell carcinoma (BCC) of the prostate. Prostatic BCCs are so rare that only approximately 100 cases have been described in the literature. Metastases is high, roughly 10%, and more than 40% of patients recur following initial therapy.
Haffner notes that, morphologically, prostatic BCCs have distinct features that differentiate them from adenocarcinomas. BCCs for instance, don't form the gland-like structures often seen in adenocarcinomas. Furthermore, there are immunohistochemical markers for proteins that are very different in their expression between adenocarcinomas carcinomas and BCCs.
Haffner and his team performed whole-genome sequencing on archival formalin-fixed, paraffin-embedded specimens of 2 patients with BCC.
Haffner and colleagues found that genomes of prostatic BCCs are characterized by an overall low copy number and mutational burden, as well as recurrent copy number loss of chromosome 16. Investigators were surprised to find that they did not observe any of the classical genomic alterations present in adenocarcinoma of the prostate.
Chromosome 16 is frequently affected by copy number changes in other tumor types. Finding such copy number chambers in a prostate cancer is “really a differentiating factor for the genomic architecture of these tumors.” The genomic alteration patterns between adenocarcinoma the prostate and prostatic BCCs are very distinct, Haffner added.
Furthermore, prostatic BCC is associated with putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD. The investigators further confirmed the mechanistic role of the CYLD protein in prostatic basal cells in vitro by demonstrating that CYLD loss leads to increased cellular proliferation. Researchers ultimately concluded that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.