Presentation Authors: Barrett McCormick*, Jad Chahoud, Frederico Netto, Priya Rao, Curtis Pickering, Curtis Pettaway, Houston, TX
Introduction: Penile Squamous Cell Carcinoma (PSCC) is rare with limited treatment options for advanced disease. There have been no published genome-wide studies on the genetic alterations of PSCCs or on the differences between human papillomavirus (HPV) positive and HPV negative PSCCs. We report the largest whole exome sequencing (WES) analysis of PSCC.
Methods: We identified 34 pts diagnosed with PSCC at the University of Texas MD Anderson Cancer Center with primary tumors or metastatic lesions sufficient for WES. Patients, tumor, and surgical characteristics were available through the MD Anderson prospective registry. Genomic DNAs from both Fresh frozen macrodissected tumors and paired-normal penile tissues were analyzed by WES.
Results: Patient's clinical characteristics are summarized in table 1. Eight of the most frequently mutated PSCC genes (NOTCH1 (35%), TP53 (35%), CDKN2A (24%), PIK3CA (21%), CASP8 (21%), FAT1 (18%), FBXW7 (15%) and EP300 (12%)) were significantly mutated in other SCC tumor types. Importantly, 8/8 and 5/8 genes were significant in head and neck SCC and cervical SCC, respectively, including 3 (CASP8, FXBW7, and EP300) genes that are only significant in these tumor types. TP53 mutations were associated with HPV negative PSCC and were absent in HPV positive SCC (P= 0.03). EP300 mutations were associated with advanced primary tumor stage. Of note, we did not identify unique mutations associated with lymph node status.
Conclusions: This is the largest systematic analyses of PSCC genomics uncovering the involvement of multiple cancer genes that are likely to be contributing to tumor development including TP53, squamous differentiation, cell cycle, and chromatin regulation. PSCCs are genomically similar to other HPV related SCC, and provide a therapeutic rationale for considering strategies successful in HPV related cancers.
Source of Funding: The University of Texas MD Anderson Cancer Center HPV Moon Shot Program