PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci. RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types. CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.
PURPOSE:Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci. RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types. CONCLUSIONS:Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.
Authors: Ahmet Murat Aydin; MacLean Hall; Brittany L Bunch; Holly Branthoover; Zachary Sannasardo; Amy Mackay; Matthew Beatty; Amod A Sarnaik; John E Mullinax; Philippe E Spiess; Shari Pilon-Thomas Journal: Int Immunopharmacol Date: 2021-02-23 Impact factor: 5.714
Authors: Jad Chahoud; William Paul Skelton; Philippe E Spiess; Christine Walko; Jasreman Dhillon; Kenneth L Gage; Peter A S Johnstone; Rohit K Jain Journal: Front Oncol Date: 2020-12-23 Impact factor: 6.244
Authors: Carlos E Stecca; Marie Alt; Di Maria Jiang; Peter Chung; Juanita M Crook; Girish S Kulkarni; Srikala S Sridhar Journal: Oncol Ther Date: 2021-01-16
Authors: Inmaculada Ribera-Cortada; José Guerrero-Pineda; Isabel Trias; Luis Veloza; Adriana Garcia; Lorena Marimon; Sherley Diaz-Mercedes; José Ramon Alamo; Maria Teresa Rodrigo-Calvo; Naiara Vega; Ricardo López Del Campo; Rafael Parra-Medina; Tarek Ajami; Antonio Martínez; Oscar Reig; Maria J Ribal; Juan Manuel Corral-Molina; Pedro Jares; Jaume Ordi; Natalia Rakislova Journal: Int J Mol Sci Date: 2021-12-27 Impact factor: 5.923
Authors: Ahmet Murat Aydin; Jad Chahoud; Jacob J Adashek; Mounsif Azizi; Anthony Magliocco; Jeffrey S Ross; Andrea Necchi; Philippe E Spiess Journal: Nat Rev Urol Date: 2020-08-18 Impact factor: 14.432