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Supplementary Figure S8 from Elucidating the Genetic Landscape of Oral Leukoplakia to Predict Malignant Transformation

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posted on 2023-04-01, 00:24 authored by Leon J. Wils, Jos B. Poell, Arjen Brink, Ilkay Evren, Elisabeth R. Brouns, Jan G.A.M. de Visscher, Elisabeth Bloemena, Ruud H. Brakenhoff

Overview of the number of CNAs and time to progression for each of the 25 progressors. The top bars show the number of CNAs. The bottom bars show the time to progression in months. CNAs = copy number aberrations.

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HANARTH foundation

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ARTICLE ABSTRACT

Oral leukoplakia is the most common oral potentially malignant disorder with an annual malignant transformation rate of 1% to 5%. Consequently, oral leukoplakia patients have a 30% to 50% lifetime risk to develop oral squamous cell carcinoma. Although risk factors for malignant transformation of oral leukoplakia have been investigated, no definitive risk stratification model has been proposed. Next-generation sequencing can elucidate the genetic landscape of oral leukoplakia, which may be used to predict the risk for malignant transformation. We investigated a retrospective cohort of 89 oral leukoplakia patients, and analyzed their oral leukoplakia lesions for the presence of genomic copy-number alterations and mutations in genes associated with oral squamous cell carcinoma. In 25 of 89 (28%) patients, oral squamous cell carcinoma developed during follow-up. Seventy-nine of 89 (89%) oral leukoplakias harbored at least one genetic event. Copy-number alterations were present in 61 of 89 (69%) oral leukoplakias, most commonly gains of chromosome regions 8q24 (46%) and 20p11 (20%) and loss of 13q12 (19%). Mutations were present in 59 of 89 (66%) oral leukoplakias, most commonly in TP53 (28%), FAT1 (20%), and NOTCH1 (13%). Genetic data were combined with the presence of dysplasia to generate a prediction model, identifying three groups with a distinct risk for malignant transformation. We provide an extensive description of genetic alterations in oral leukoplakia and its relation to malignant transformation. On the basis of our data we provide a model for the prediction of malignant transformation of oral leukoplakia using dysplasia and genetic markers.

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