Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

Abstract

BackgroundThe mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.MethodsSamples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.ResultsTongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.ConclusionsWe suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.

Chromosomal Instability, DNA Index, Dysplasia, and Subsite in Oral Premalignancy as Intermediate Endpoints of Risk of Cancer

“…The second surrogate endpoint was based on the subsite of the OPMDs considering that the tongue and FOM subsites were qualified predictors of risk of cancer development in a recent study involving a prospective cohort of 296 patients with OPMDs with mild/moderate dysplasia (17,57,58). Distinctive features of chromosomal aberrations and increased incidence of DNA aneuploidy for the tongue OPMDs with respect to the OPMDs in all the other oral subsites were also reported in a recent study from our group, which suggested that these patients should receive a distinctive special attention (15).…”

“…Moreover, OPMDs are not the only precursors of OSCCs (2-6, 52) because OSCCs may also develop from ONAMFs characterized by absence of dysplasia and with a transformation rate that still remains to be evaluated. The genomic characteristics of ONAMFs and OPMDs were recently investigated using array-comparative genomic hybridization and hr-DNA-FCM in a small number of cases (15,16). Presently, 135 ONAMFs and 195 OPMDs (171 nondysplastic and 24 dysplastic) for a consecutive series of 165 patients with OMPD were investigated by hr-DNA-FCM.…”

“…Genetic, epigenetic, and genomic aberrations in oral normal-appearing mucosa fields (ONAMFs), oral potentially malignant disorders (OPMDs; mostly leukoplakias), and oral squamous cell carcinomas (OSCCs) have been the subject of extensive studies and reviews (3,(10)(11)(12)(13)(14)(15)(16). The potential of these aberrations to represent risk biomarkers for OPMD progression still remains unproven.…”

“…35) and investigated the association of the DI values with high-risk oral sites (tongue and floor of the mouth; FOM; ref. 15) and dysplasia in OPMDs as surrogate endpoints of risk of OSCC development.…”

High‐resolution DNA content analysis of microbiopsy samples in oral lichen planus

“…The present study was undertaken within the frame of a wider project carried on over the last 6 years and aiming to assess the DNA‐aneuploidy point prevalence and role among oral potentially malignant disorders and SCC using fresh/frozen samples coupled with high‐resolution and high‐sensitivity DNA‐FCM (Pentenero et al , , ,b, ; Donadini et al , ; Castagnola et al , ; Giaretti et al , ,b, ). The preparation of the nuclei suspension from fresh/frozen material and DAPI staining allowed us to routinely obtain G0/G1 DNA diploid control nuclei with CV values as low as 1% and an extremely low background, thus allowing the detection of DNA near‐diploid aneuploid sublines with DNA changes as low as 2.5% with respect to the DNA diploid status (Donadini et al , ).…”