AUTHOR=Cao Jian , Yang Chun-He , Han Wei-Qing , Xie Yu , Liu Zhi-Zhong , Jiang Shu-Suan 

TITLE=Correlation Between the Evolution of Somatic Alterations During Lymphatic Metastasis and Clinical Outcome in Penile Squamous Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.641869

DOI=10.3389/fonc.2021.641869

ISSN=2234-943X

ABSTRACT=<p>Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were <italic>TP53</italic> (13/32), <italic>NOTCH1</italic> (12/32), <italic>CDKN2A</italic> (11/32), <italic>TTN</italic> (9/32) and <italic>FAT1</italic> (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While <italic>CDKN2A</italic> was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including <italic>TP53</italic> (9/14 <italic>vs.</italic> 4/18, p = 0.029) and <italic>GBF1</italic> (4/14 <italic>vs.</italic> 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including <italic>PIK3CA</italic> (Hazard ratio [HR] = 4.15, p = 0.029), <italic>CHD7</italic> (HR = 4.82, p = 0.032) and <italic>LAMC3</italic> (HR = 15.9, p &lt; 0.001). <italic>PIK3CA</italic> and <italic>LAMC3</italic> held a higher prevalence in patients with LNM compared to those without LNM (<italic>PIK3CA</italic>: 3/14 <italic>vs.</italic> 1/18, <italic>LAMC3</italic>: 2/14 <italic>vs.</italic> 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.</p>