A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia

Abstract

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high‐risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high‐risk OL groups for follow‐up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

Comparing Length and Telomere Expression at Oral Precancerous and Cancerous Stages

“…They established the important clinical practicality of telomerase activation as a useful indication for the diagnosis and its efficacy as a marker for the OSCC prognosis. According to Pal et al, the method of analyzing TL attrition of the oral mucosa, eradicating the necessity of the external reference DNA, would facilitate the TL data unanimously (36). Hence, it would serve as a significant marker for defining highrisk oral precancerous groups for a further follow-up program.…”

A Review of the Repair of DNA Double Strand Breaks in the Development of Oral Cancer

“…In non-proliferating cells, quiescent cells, or terminally differentiated cells, a DDR can be activated independently of telomere length. Telomere dysfunction combined with the activation of the DDR is thought to be a critical early event in the development of human cancer [103], a proposal that is supported by data from pre-cancer models [104], including OPMD [105,106].…”