Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa

Noninvasive brush biopsies of normal-appearing oral mucosa revealing premalignant clonal expansions (*TP53*, CNVs) in Fanconi anemia patients

Fanconi anemia, a head and neck squamous cell carcinoma predisposition syndrome caused by defective DNA interstrand crosslink repair, serves here as a model to profile the premalignant field via noninvasive oral mucosa brush biopsies. In clinically normal mucosa, pathogenic TP53 variants were detected in 26% of cases and copy number alterations in 60.5%, defining candidate biomarkers of early clonal evolution. The authors also report somatic reversion of a pathogenic FANCB variant, suggesting protective genomic self-correction. Repeated noninvasive sampling opens the way to surveillance and preventive strategies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

An appealing approach: a painless, repeatable brush to monitor the oral cancerization field of Fanconi patients, a population at extreme squamous cell carcinoma risk. If early detection of mutated TP53 clones truly precedes transformation, this is a valuable risk-stratification tool in a setting where surveillance remains largely clinical. To be confirmed beyond preprint status and on longitudinal cohorts.