1. Clonal Relationship Between Lichen Sclerosus, Differentiated Vulvar Intra-epithelial Neoplasia and Non HPV-related Vulvar Squamous Cell Carcinoma
- Author
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Michelle van der Linden, Angela A.G. van Tilborg, Anne-Floor W. Pouwer, Johan Bulten, Jiangyan Yu, Joanne A. de Hullu, Roland P. Kuiper, Astrid Eijkelenboom, Leon F.A.G. Massuger, Eveline J. Kamping, Jayne Y. Hehir-Kwa, Koen M. Hendriks, and Loes C.G. van den Einden
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,endocrine system ,Vulvar Squamous Cell Carcinoma ,Copy number analysis ,Lichen sclerosus ,Biochemistry ,Somatic evolution in cancer ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Genetics ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Medicine ,Humans ,Molecular Biology ,Aged ,Vulvar neoplasm ,Aged, 80 and over ,Vulvar Lichen Sclerosus ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Vulvar Neoplasms ,business.industry ,Vulvar cancer ,Middle Aged ,medicine.disease ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Lichen Sclerosus et Atrophicus ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,medicine.symptom ,business ,Carcinoma in Situ ,Research Article - Abstract
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.
- Published
- 2020