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240 Distinct patterns of copy number aberrations in penile cancer
240
Distinct patterns of copy number aberrations in penile cancer Eur Urol Suppl 2016;15(3);e240
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Rodney S. 1 , Feber A. 1 , Arya M. 2 , De Winter P. 1 , Saqib M. 1 , Nigam R1 , Malone P. 1 , Tan S. 1 , Christodoulidou M. 1 , Sahdev V. 1 , Lechner M. 3 , Freeman A. 4 , Jameson C.1 , Muneer A. 2 , Beck S. 5 , Kelly J. 1 , Simon Rodney 1 University
College London, Dept. of Surgery and Interventional Sciences, London, United Kingdom, 2 University College London Hospital,
Dept. of Urology, London, United Kingdom, 3 University College London Hospitals, Dept. of Histopathology, London, United Kingdom, 4 University
College London Hospital, Dept. of Histopathology, London, United Kingdom, 5 University College London, UCL Cancer Institute,
London, United Kingdom INTRODUCTION & OBJECTIVES: In Europe penile cancer (PeCa) is a rare disease, with an incidence of approximately 1.5 per 100,000 males rising to 4.4 per 100,000 men in South America and Africa. PeCa therefore represents a significant global health problem with devastating consequences. Due to the rarity of the disease there is a paucity of knowledge as to the genetic drivers of the disease with poor outcomes for patients in whom lymph node metastases are present. Our previous work demonstrated a large range of epigenetic drivers in this disease. We now wish to examine the role that copy number aberrations play in driving the oncogenesis of the disease. MATERIAL & METHODS: High density genome wide methylation arrays were used as previously validated to assess copy number variation using the conumee package in R. Samples from twenty four patients with primary squamous cell penile carcinoma were used in this analysis. Further analysis was subsequently performed using GISTIC (a tool to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth). RESULTS: Significant amplifications were found including 4p15.2, 9p22.3, 19p13.2, 19p12 and 19q13.2. Significant deletions were found at 4q35.2, 6q22.31, 6q27, 7q36.1, 11p15.4, 11q12.1, 11q23.3, 13q13.3, 15q11.2 and 21q22.11. Distinct patterns of copy number gains were noted for both the HPV positive samples (1p36.11, 3q26.2, 6p22.1) and lymph node positive samples (3q26.2 and 11q22.2). These copy number alterations included many known oncogenes including MYC and FGFR3 as well as tumour suppressors CDKN2A, CCND1, RB1 and p53. CONCLUSIONS: This new study interrogated 24 penile cancer genomes using high density genome wide methylation arrays. We present distinct patterns of copy number variations for both HPV positive and lymph node positive samples. This both corroborates previous findings of a defined amplification at 19q13 but also adds further novel variations in both HPV positive and lymph node negative subsets of disease. This new information will be helpful for both future functional work on uncovering the drivers of penile carcinoma and for development of novel biomarkers to help predict lymph node metastases.
Distinct patterns of copy number aberrations in penile cancer Eur Urol Suppl 2016;15(3);e240
Print! Print!
Rodney S. 1 , Feber A. 1 , Arya M. 2 , De Winter P. 1 , Saqib M. 1 , Nigam R1 , Malone P. 1 , Tan S. 1 , Christodoulidou M. 1 , Sahdev V. 1 , Lechner M. 3 , Freeman A. 4 , Jameson C.1 , Muneer A. 2 , Beck S. 5 , Kelly J. 1 , Simon Rodney 1 University
College London, Dept. of Surgery and Interventional Sciences, London, United Kingdom, 2 University College London Hospital,
Dept. of Urology, London, United Kingdom, 3 University College London Hospitals, Dept. of Histopathology, London, United Kingdom, 4 University
College London Hospital, Dept. of Histopathology, London, United Kingdom, 5 University College London, UCL Cancer Institute,
London, United Kingdom INTRODUCTION & OBJECTIVES: In Europe penile cancer (PeCa) is a rare disease, with an incidence of approximately 1.5 per 100,000 males rising to 4.4 per 100,000 men in South America and Africa. PeCa therefore represents a significant global health problem with devastating consequences. Due to the rarity of the disease there is a paucity of knowledge as to the genetic drivers of the disease with poor outcomes for patients in whom lymph node metastases are present. Our previous work demonstrated a large range of epigenetic drivers in this disease. We now wish to examine the role that copy number aberrations play in driving the oncogenesis of the disease. MATERIAL & METHODS: High density genome wide methylation arrays were used as previously validated to assess copy number variation using the conumee package in R. Samples from twenty four patients with primary squamous cell penile carcinoma were used in this analysis. Further analysis was subsequently performed using GISTIC (a tool to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth). RESULTS: Significant amplifications were found including 4p15.2, 9p22.3, 19p13.2, 19p12 and 19q13.2. Significant deletions were found at 4q35.2, 6q22.31, 6q27, 7q36.1, 11p15.4, 11q12.1, 11q23.3, 13q13.3, 15q11.2 and 21q22.11. Distinct patterns of copy number gains were noted for both the HPV positive samples (1p36.11, 3q26.2, 6p22.1) and lymph node positive samples (3q26.2 and 11q22.2). These copy number alterations included many known oncogenes including MYC and FGFR3 as well as tumour suppressors CDKN2A, CCND1, RB1 and p53. CONCLUSIONS: This new study interrogated 24 penile cancer genomes using high density genome wide methylation arrays. We present distinct patterns of copy number variations for both HPV positive and lymph node positive samples. This both corroborates previous findings of a defined amplification at 19q13 but also adds further novel variations in both HPV positive and lymph node negative subsets of disease. This new information will be helpful for both future functional work on uncovering the drivers of penile carcinoma and for development of novel biomarkers to help predict lymph node metastases.