Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa
Berger, T.; Donovan, F. X.; Lin, Y.-C.; Soma, S.; May, F.; Bhadresha, K.; Krieg, C.; Giri, N.; McReynolds, L. J.; Filie, A.; Khavandgar, Z.; Laronde, D. M.; Guillaud, M.; Savage, S. A.; Kutler, D. I.; Crismani, W.; Velleuer, E.; Uppgaard, R.; Harper, U. L.; Alston, K. O.; Thomas, J. W.; Auerbach, A. D.; Chandrasekharappa, S. C.; Smogorzewska, A.
Show abstract
Head and neck squamous cell carcinoma (HNSCC) evolves through stepwise clonal expansion within genetically altered mucosa fields, yet actionable biomarkers remain undefined. Leveraging Fanconi anemia (FA), a cancer predisposition syndrome with extreme HNSCC risk due to defective DNA interstrand crosslink repair, we profiled premalignant changes in the oral cavity using noninvasive brush biopsies. Consistent with our prior demonstration of genomic instability in FA-associated SCCs, we detected pathogenic TP53 variants in 26% and copy number alterations in 60.5% in clinically normal-appearing oral mucosa of individuals with FA. These subclinical clonal expansions define candidate biomarkers of early clonal evolution amenable to serial sampling for risk stratification and prevention studies. Since FA-associated SCCs share genomic features with sporadic HNSCC, these findings may extend to the broader population. We also identify somatic reversion of a pathogenic FANCB variant, providing evidence of genomic self-correction and suggesting a potential avenue for gene-based cancer prevention in FA.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Recurrent human papillomavirus-related head and neck cancer undergoes metabolic re-programming and is driven by oxidative phosphorylation 92%
- Interactions in CSF1-driven Tenosynovial Giant Cell Tumors 91%
- Zinc Finger MYND-Type Containing 8 (ZMYND8) is epigenetically regulated in mutant Isocitrate Dehydrogenase 1 (IDH1) glioma to promote radioresistance 91%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- A transgenic line that reports CSF1R protein expression provides a definitive marker for the mouse mononuclear phagocyte system 90%
- Single cell based high-throughput Ig and TCR repertoire sequencing analysis in rhesus macaques 89%
- A defect in thymic tolerance causes T cell-mediated autoimmunity in a murine model of COPA syndrome 89%
Similar papers in this journal
- Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Cancers Identifies KMT2C as a Potential Tumor Suppressor 93%
- Comprehensive Study of Germline Mutations and Double-Hit Events in Esophageal Squamous Cell Cancer 93%
- Detection of Somatic Copy Number Deletion of CDKN2A Gene for Clinical Practices Based on Discovery of A Base-Resolution Common Deletion Region 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.