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Oral keratosis of unknown significance shares genomic overlap with oral dysplasia
Author(s) -
Villa Alessandro,
Hanna Glenn J.,
Kacew Alec,
Frustino Jennifer,
Hammerman Peter S.,
Woo SookBin
Publication year - 2019
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.13155
Subject(s) - actinic keratosis , medicine , dysplasia , leukoplakia , keratosis , dermatology , epithelial dysplasia , clinical significance , hyperkeratosis , cancer , basal cell
Objectives To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively. Methods Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer‐associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate‐to‐severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population. Results Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow‐up of 67 (range 22–144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration. Conclusions Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.