Introduction:

In Europe penile cancer (PeCa) is a rare disease, with an incidence of approximately 1.5 per 100,000 males. Due to the rarity of the disease there is a paucity of knowledge of its genetic drivers. Our previous work demonstrated a large range of epigenetic drivers. We now present the role that copy number aberrations play in driving the oncogenesis of penile cancer.

Patients & Methods:

High density genome wide methylation arrays were used to assess copy number variation using the conumee package in R. Samples from twenty four patients with squamous cell penile carcinoma were used. Further analysis was performed using GISTIC (a tool to identify genes targeted by somatic copy-number alterations 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, KRAS 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.