Exome sequencing of oral leukoplakia and oral squamous cell carcinoma implicates DNA damage repair gene defects in malignant transformation

Malignant transformation rate of oral leukoplakia in an Australian population

“…This has been performed in oesophageal SCC where mutational profiles were compared between matched sets of pre-malignant lesions and their matching SCCs, as well as with dysplastic samples from patients without cancer 34. More recently, we have shown that exomic sequencing of dysplastic and non-dysplastic leukoplakia has demonstrated that progressive leukoplakia can be differentiated from non-progressive leukoplakia using the frequency of exomic variants, particularly in DNA damage repair pathway genes, implicating the Fanconi anemia/BRCA double-strand break pathway in malignant transformation of OED to OSCC 35. A greater understanding of the molecular pathways involved in oral carcinogenesis would also allow for more effective and personalised treatment of potentially malignant lesions such as OLK.…”

World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia and proliferative verrucous leukoplakia—A systematic review of retrospective studies

“…Some studies analysed multiple candidate biomarkers, and collectively, the 54 studies identified 109 unique biomarkers (Table 2) representing a range of biological categories, including transmembrane receptors, transporters, growth factors and enzymes among others. Biomarkers were stratified by hallmarks of cancer (Farah et al., 2019) and were generally categorized as follows: Stem cell markers (e.g. ABCG2, BMI‐1, ALDH1, CD133, SNAI1, Axin2), cellular adhesion and migration markers (e.g.…”

“…Achievement of risk stratification and precision approaches for OL and PVL management potentially lies in biomarker discovery. While stratifying biomarkers according to the hallmarks of cancer (Farah et al., 2019), this current systematic review focused specifically on retrospective studies incorporating a longitudinal study design to assess the evidence to support a potential role for application of prognostic biomarkers to stratify risk prediction for MT‐OL and MT‐PVL. Each hallmark included multiple biomarker candidates, further complicating distillation of appropriate biomarkers for MT‐OL and MT‐PVL.…”

“…The evidence base continues to reflect that genetic susceptibility, represented by loss of heterozygosity, chromosomal instability, CNV and copy number alteration, may underlie predisposition for MT‐OL (Cervigne et al., 2014; Siebers et al., 2013). Thus, monitoring for genetic susceptibility either alone or in combination with other candidate biomarkers may be used to: (a) predict status of OL, (b) stratify patient cohorts at low‐ or high‐risk MT‐OL and (c) ultimately inform precision medicine approaches to condition management (Farah et al., 2019; Zhang et al., 2012).…”

“…The presence or the degree of OED are not sufficiently predictive of malignant transformation (Dost et al., 2014; Holmstrup, Vedtofte, Reibel, & Stoltze, 2007) with up to 3.5% of non‐dysplastic lesions developing oral squamous cell carcinoma (OSCC) (Hsue et al., 2007). A subset of OL presenting with “genotypic dysplasia” lacking histopathological evidence of “phenotypic dysplasia” was first identified by Farah et al (2019) in a study exploring transcriptomic differences between dysplastic and non‐dysplastic OL (Farah & Fox, 2019). Additionally, leukoplakia without dysplasia (termed keratosis of unknown significance [KUS] by some authors) has been shown to share genomic features with dysplastic OLs (Villa, Hanna, et al, 2019).…”