Cumulation of TP53 Mutations and p16INK4A/ p15INK4B Homozygous Deletions in Human Papilloma Virus Type 16 Positive Scrotal Cancer

Abstract

Scrotal cancer is the first described occupational cancer. The frequency of occupation-related scrotal cancer is very rare because of better hygiene and protective clothing. Human papilloma viruses (oncogenic types 16 and 18) were reported as the causative agents in the pathogenesis of scrotal cancers. E5, E6, and E7 proteins, expressed by human papilloma virus type 16, affect the cell cycle at the G1 checkpoint. TP53, p16 INK4A , and p15 INK4B were reported as the transcription factors that regulate the cell cycle on the same pathway. Here, the mutation pattern of TP53, p16 INK4A , and p15 INK4B genes and the homo/hemizygous deletion patterns of p16 INK4A /p15 INK4B genes are presented in four scrotal carcinoma cases. The results were correlated with the findings of oncogenic human papilloma viruses (types 16 and 18) in this panel. In two of four case, human papilloma virus type 16 was observed. Homozygous deletion in p16 INK4A /p15 INK4B genes and a codon 259 missense point mutation (GAC →TAC; Asp →Tyr) in the TP53 gene were observed in one human papilloma positive scrotal carcinoma case. The homozygous deletion in p16 INK4A /p15 INK4B genes was observed in another human papilloma positive scrotal carcinoma case. The cumulation of TP53 mutations and p16 INK4A /p15 INK4B homozygous deletions in human papilloma virus type 16 positive scrotal carcinoma cases indicate that the alterations of TP53, p16 INK4A , and p15 INK4B genes have an important role in the progression of scrotal cancers, as well as other factors. The survival rate for the two human papilloma virus type 16 positive patients who had a TP53 mutation or p16 INK4A /p15 INK4B homozygous deletion or both was lower than that for the human papilloma virus type 16 negative cases who had no TP53, p16 INK4A , and p15 INK4B mutation. The molecular alteration of TP53, p16 INK4A , and p15 INK4B genes may be useful as a prognostic marker in scrotal cancer.