.png){kind=icon}
.png){kind=icon}
Return
Impact of Copy-number Alterations on Human Papillomavirus (HPV)-Induced and HPV-Independent Penile Cancers
.png){kind=icon}
OA
AI
M
S
K
DOI：10.1016/j.labinv.2026.106129.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Penile squamous cell carcinomas (SCC) develop via a transforming human papillomavirus (HPV) infection or independent of HPV. We assessed the role of copy-number alterations (CNA) affecting chromosome arms, oncogenes and tumor suppressor genes (TSG) in 121 penile SCC (52% HPV-associated and 48% HPV-independent) using shallow whole-genome sequencing. CNA were common and complex, with frequent co-occurrences. Neither etiology had exclusive CNA. Arm-level changes included gains of 3q and 8q (48% each), 1q (36%), 1p (26%), 9q (36%) and 9p (31%) and losses of 19p (48%), 8p (44%), 1q (36%), and 3p (33%) of SCC. Oncogene amplifications included broad 3q alterations affecting TP63, SOX2, PIK3CA (43%) and 8q including MYC, HEY, RAD21 (40%). Homozygous deletions affected WRN, NRG1 (8p;29%), BAP1, FANCD2, VHL (3p) and ARHGEF12, BCL9L, ATM (11q22/23) in 19% each. CNA affecting TP53, CDKN2A/B, CDKN1A/B, and RB1 occurred in similar numbers in HPV-induced (16%) and HPV-independent SCC (24%) quite in contrast to TSG somatic mutations exclusive to HPV-independent SCC associated with lichenoid dermatoses. HPV-induced SCC had more 1p amplifications (adj. p=.003), while HPV-independent SCC carried more 8q full-arm gains (adj. p=.00003), amplifications of oncogenes on 8q (adj. p=.006) including MYC and homozygous deletions of 8p (adj. p=.03). MYC amplifications coincided with an increased fraction of genome altered indicative for genomic instability (p=.00001). EGFR amplifications dominated in HPV-negative wild-type TP53/CDKN2A SCC without dermatoses. Together with mutations in PIK3CA, HRAS and FGFR3 they represent an alternative RTK/Ras/PI3K-mediated carcinogenesis pathway. More than half of advanced SCC irrespective of etiology harbored targetable CNA such as EGFR, MTAP, ATM.
Keywords:
penile squamous cell carcinoma
copy-number alterations
human papillomavirus
oncogenes
tumor suppressor genes
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
IF:
4.2
Papers:
5.4K
Citations:
1.1W
Organization
No organization information available
Cited Papers