Management of Fanconi Anemia patients with head and neck carcinoma: Diagnosis and treatment adaptation.

Fanconi anemia (FA) is a rare genetic disease that is mostly transmitted, according to a recessive model with biallelic germline alterations in one of the 22 genes of the FA pathway, or monoallelic alteration of the 23rd FA gene (RAD51). The FA pathway is implicated in interstrand DNA crosslink repair, induces genome stability, and is a potent driver of tumorigenesis. Patients with FA have a 500 to 1000-fold increased risk of developing head and neck squamous cell carcinoma (HNSCC). Patients with FA developing an HNSCC, usually have severe radiation toxicities. In this context, the modalities of radiation therapy should be adapted. Some patients with FA present a milder phenotype, especially in the case of medullary FA gene spontaneous reversion. Therefore, in an unusual context of HNSCC, such as no risk factors or a young age, it may be very useful to search anemia or development abnormalities, that may unravel a yet undiagnosed FA disease. Besides, in some young patients with HNSCC who did not suffer from FA, a monoallelic germline alteration in an FA gene could be combined with a second risk factor such as HPV infection or APOBEC alteration. Although several in vitro studies showed that normal cells with monoallelic FA gene alteration may have a particular radiosensitivity, these observations have not been confirmed in vivo in FA heterozygotes patients. Finally, some somatic activating alterations have also been found in HSNCC tumor samples and could be associated with radioresistance.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.