Pathological variants in HPV-independent vulvar tumours
Sanja A Farkas1, Alvida Qvick2, Gisela Helenius3
1Department of Laboratory Medicine, Clinical Pathology and Genetics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. sanja.farkas@oru.se.
Scientific Reports
|January 9, 2025
Summary
Human papillomavirus (HPV)-independent vulvar tumors show greater molecular heterogeneity and more single nucleotide variants (SNVs) than HPV-associated tumors. HPV-associated vulvar cancers exhibit more frequent gene amplifications, indicating distinct genetic pathways.
Area of Science:
- Gynecologic Oncology
- Cancer Genomics
- Human Papillomavirus (HPV) Research
Background:
- Vulvar cancer is a rare gynecologic malignancy.
- Human papillomavirus (HPV) infection is a known cause of vulvar cancer.
- Distinct molecular pathways are suspected for HPV-associated versus HPV-independent vulvar tumors, necessitating further research for targeted therapies.
Purpose of the Study:
- To investigate and compare the mutational landscape of HPV-associated and HPV-independent vulvar tumors.
- To identify distinct genetic alterations and biological mechanisms underlying different vulvar cancer subtypes.
- To provide insights for developing individualized treatment strategies.
Main Methods:
- Analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples from 32 vulvar cancer patients (16 HPV-negative, 16 HPV-associated).
- Utilized the Oncomine™ Comprehensive Assay v3 for detecting genetic variants across 161 tumor-relevant genes (DNA and RNA analysis).
- Employed VarSome Clinical software with a custom filter for variant analysis and classification.
Main Results:
- HPV-negative tumors exhibited a higher number of single nucleotide variants (SNVs) and a greater fraction of variants of unknown significance (VUS) or pathogenic variants compared to HPV-associated tumors.
- HPV-associated tumors showed more frequent copy number variations (CNVs), particularly in genes like cMYC, CDK2, and CDK4.
- Commonly mutated genes in HPV-independent tumors included TP53, POLE, and BRCA2. Fusion genes and pathway alterations (PI3K/AKT/mTOR1, cell cycle regulation) were observed in both groups.
Conclusions:
- Vulvar cancer presents with diverse genetic variations, with HPV-independent tumors being molecularly heterogeneous and HPV-associated tumors showing more gene amplifications.
- The PI3K/AKT/mTOR1 and cell cycle regulation pathways are implicated in both vulvar cancer types.
- The DNA repair gene POLE is a potential target across both HPV-associated and independent vulvar cancers.
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