Copy Number Analysis Reveal Genetic Risks of Penile Cancer.

Yongbo Yu,Haitao Niu,Jianfeng Zhang,Yuanbin Chen,Meilan Wang,Chengwen Gao,Xiaocheng Ma,Hang Yuan,Shuaihong Liu,Zhiqiang Li

doi:10.3389/fonc.2020.596261

Abstract

ObjectivesTo evaluate copy number alterations (CNAs) in genes associated with penile cancer (PeC) and determine their correlation and prognostic ability with PeC.MethodsWhole-exome sequencing was performed for tumor tissue and matched normal DNA of 35 patients diagnosed with penile squamous cell carcinoma from 2011 to 2016. Somatic CNAs were detected using the Genome Analysis Toolkit (GATK). Retrospective clinical data were collected and analyzed. All the data were statistically analyzed using SPSS 16.0 software. The cancer-specific survival rates were estimated by Kaplan-Meier curves and compared with the log-rank test.ResultsCNAs in the MYCN gene was detected in 19 (amplification: 54.29%) patients. Other CNAs gene targets were FAK (amplification: 45.72%, deletion: 8.57%), TP53 (amplification: 2.86%, deletion: 51.43%), TRKA (amplification: 34.29%, deletion: 2.86%), p75NTR (amplification: 5.71%, deletion: 42.86%), Miz-1 (amplification: 14.29%, deletion: 20.00%), Max (amplification: 17.14%, deletion: 2.86%), Bmi1 (amplification:14.29%, deletion: 48.57%), and MDM2 (amplification: 5.71%, deletion: 45.72%). The CNAs in MYCN and FAK correlated significantly with patient prognosis (P<0.05). The 3-year Recurrence-free survival rate was 87.10% among patients followed up. The 5-year survival rate of patients with MYCN amplification was 69.2%, compared to 94.4% in the non-amplification group. The 5-year survival rate of patients with FAK amplification was 65.6%, compared to 94.7% in the non-amplification group. The PPI network showed that TP53 and MYCN might play meaningful functional roles in PeC.Conclusion MYCN and FAK amplification and TP53 deletion were apparent in PeC. MYCN and TP53 were hub genes in PeC. MYCN and FAK amplification was also detected and analyzed, and the findings indicated that these two genes are predictors of poor prognosis in PeC.

Highlights

Penile cancer (PeC) is a rare and aggressive malignant tumor that accounts for less than 1% of carcinomas in males in the United States [1]
Primary treatment for PSCC included partial or radical penectomy with concomitant inguinal lymph node dissection (ILD), which included ipsilateral or ilioinguinal lymphadenectomy via contralateral superficial inguinal or ilioinguinal dissection according to the clinical condition
All patients were diagnosed with penile squamous cell carcinoma

Summary

Introduction

Penile cancer (PeC) is a rare and aggressive malignant tumor that accounts for less than 1% of carcinomas in males in the United States [1]. The regional differences in incidence are significant, with the high incidence in the developing countries (2.8–6.8 per 100,000), where the low rate of neonatal circumcision and socioeconomic conditions make the patients vulnerable to a variety of risk factors. Various have been identified, including lack of circumcision, phimosis, smoking, balanitis, obesity, lichen sclerosus, and psoralen UV-A phototherapy, contributing to the courses of PeC. Several studies have detected somatic changes that arise in [3,4,5], but few of them were based on whole-exome sequencing [5]. Our previous study has performed a wholeexome sequencing analysis of PeC, and identified recurrent mutations in 11 genes [6]

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