Errazquin, R.; Carrasco, E.; Del Marro, S.; Suñol, A.; Peral, J.; Ortiz, J.; Rubio, J.C.; Segrelles, C.; Dueñas, M.; Garrido-Aranda, A.; Alvarez, M.; Belendez, C.; Balmaña, J.; Garcia-Escudero, R. Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma. Cancers2023, 15, 1871.
Errazquin, R.; Carrasco, E.; Del Marro, S.; Suñol, A.; Peral, J.; Ortiz, J.; Rubio, J.C.; Segrelles, C.; Dueñas, M.; Garrido-Aranda, A.; Alvarez, M.; Belendez, C.; Balmaña, J.; Garcia-Escudero, R. Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma. Cancers 2023, 15, 1871.
Errazquin, R.; Carrasco, E.; Del Marro, S.; Suñol, A.; Peral, J.; Ortiz, J.; Rubio, J.C.; Segrelles, C.; Dueñas, M.; Garrido-Aranda, A.; Alvarez, M.; Belendez, C.; Balmaña, J.; Garcia-Escudero, R. Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma. Cancers2023, 15, 1871.
Errazquin, R.; Carrasco, E.; Del Marro, S.; Suñol, A.; Peral, J.; Ortiz, J.; Rubio, J.C.; Segrelles, C.; Dueñas, M.; Garrido-Aranda, A.; Alvarez, M.; Belendez, C.; Balmaña, J.; Garcia-Escudero, R. Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma. Cancers 2023, 15, 1871.
Abstract
Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.
Keywords
Fanconi anemia; oral cancer; oral potentially malignant lesion; liquid biopsy; saliva; oral rinse; plasma; next generation sequencing; cancer gene panel; early diagnosis; diagnostic test; deep sequencing
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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