Presentation Authors: Priyanka Kancherla*, Syracus, NY, Joseph M Jacob, Rubin Pinkhasov, Oleg Shapiro, Nick Liu, Syracuse, NY, Laurie M Gay, Brian Michael Alexander, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Cambridge, MA, Shakti Ramkissoon, Boston, MA, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Cambridge, MA, Venkataprasanth P Reddy, Westwood, KS, Vincent A. Miller, Cambridge, MA, Robert J. Corona, Jeffrey S. Ross, Gustavo de La Roza, Gennady Bratslavsky, Joseph Jacob, Syracuse, NY
Introduction: Relapsed and metastatic penile (mPSCC) and uterine cervical squamous cell carcinoma (mCSCC) are aggressive forms of malignancy with currently limited systemic treatment options. We performed a comprehensive genomic profiling (CGP) study to compare the genomic alterations (GA) and their potential impact on targeted and immunotherapy options.
Methods: 78 cases of metastatic mPSCC and 604 cases of mCSCC underwent CGP on a minimum of 50 ng of DNA using a hybrid-capture, adaptor ligation-based next-generation sequencing assay with a mean coverage depth of >500X. The results were analyzed for all classes of genomic alterations (GA), including base substitutions, insertions and deletions (short variants; SV), fusions, and copy number changes including amplifications (amp) and homozygous deletions. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci.
Results: The median age of the men with mPSCC was higher than the women with mCSCC. The HPV+/CDKN2A- status was significantly more frequent in the mCSCC than mPSCC cases. The GA/tumor frequencies were similar for both tumor types. TP53 mutations were more common in mPSCC, which may be associated with the loss of an original HPV+ status. TERT, NOTCH1 and FAT1 GA were more frequent in mPSCC whereas PIK3CA GA were more common in mCSCC. MTOR pathway targets (GA in STK11, FBXW7 and PTEN) were more common in mCSCC. MSI-High status was extremely rare in all cases, but the relatively high frequencies of TMB > 10/20 mut/Mb in both mPSCC and mCSCC were noteworthy. Examples of patients with mCSCC and mPSCC responding to targeted and immunotherapies will be presented.
Conclusions: Although mCSCC and mPSCC share a variety of genomic features, the 2 tumor types can nonetheless be sharply differentiated on CGP. The TP53, CDKN2A and HPV status of the tumor types differ significantly with viral identification much higher in the mCSCC group. There are opportunities for targeted therapies in both groups predominantly identified in the MTOR pathway. The relatively high numbers of cases with significantly elevated TMB in both mPSCC and mCSCC suggest that immunotherapies might be of benefit in a subset of patients.