Journal
CANCER GENOMICS & PROTEOMICS
Volume 17, Issue 2, Pages 151-160Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/cgp.20175
Keywords
Vulvar cancer; vulvar neoplasms; squamous cell carcinoma; lichen sclerosus; vulvar lichen sclerosus; differentiated vulvar intraepithelial neoplasia; clonal evolution
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Funding
- Stichting Ruby and Rose
- Radboud Oncology Funding
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Background/Aim: Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions. Materials and Methods: DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53. Results: Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%. Conclusion: Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS.
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