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Molecular, genomic and mutational landscape of oral leukoplakia.

Oral leukoplakia (OLK) and its more aggressive clinical variant proliferative verrucous leukoplakia (PVL) remain enigmatic disorders clinically and histopathologically. Despite decades of research into both, there has been only incremental advancement in our understanding of their aetiology and pathogenesis and only minimal improvement in effective management strategies. Currently, no specific prognostic genetic or molecular marker has been reported for leukoplakia. There is, however, an emerging body of evidence characterising the genomic and transcriptomic profile of OLK. Regardless of the significance of cellular and architectural features of OLK and PVL, it is clear from studies reported in this review that new emerging evidence points to the presence of premalignant molecular subtypes of leukoplakia which require further investigation. This up-to-date review explores the contemporary genomic, transcriptomic and mutational landscape of leukoplakia broadly, discusses concepts that may not be widely recognised or accepted and purposefully highlights studies with juxtaposed findings in an effort to challenge dogma. It also highlights the urgent need for a concerted international effort of original collaborative research which will only occur by pooling collective efforts, resources and intellect to define the molecular fingerprint of this enigmatic disorder, in the hope it will better inform diagnosis, stratification and treatment.