Fanconi anemia (FA) is a rare genome instability syndrome characterized by progressive bone marrow failure and predisposition to cancer, especially head and neck squamous cell carcinoma. Surgical resection is the standard of care for solid tumors, as patients with FA do not tolerate genotoxic chemotherapies or radiation, leading to poor prognosis. It is therefore imperative to develop chemoprevention strategies such as the identification of novel biomarkers to detect the formation of the tumor before its emergence and to use them in clinical trials aimed to counteract genome instability of patients with FA in tissues at risk. Micronuclei (MN) are chromosome fragments that are left behind in anaphase and appear in daughter cells as small additional nuclei. In this work, we analyzed MN frequencies in exfoliated buccal cells from 40 patients with FA and 24 controls. We found that MN frequency was significantly increased in the FA cohort indicating that we can detect chromosome fragility in patients with FA in basal conditions and in a tissue that is divided in vivo. Consequently, the MN assay in exfoliated buccal cells of patients with FA could be used in cancer risk studies and clinical trials aimed to identify cancer chemopreventive drugs.

中文翻译：

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范可尼贫血患者颊上皮的染色体脆性。

范可尼贫血（FA）是一种罕见的基因组不稳定综合征，其特征是进行性骨髓衰竭和易患癌症，尤其是头颈部鳞状细胞癌。手术切除是治疗实体瘤的标准，因为FA患者不耐受基因毒性化学疗法或放射线治疗，导致预后不良。因此，必须开发化学预防策略，例如鉴定新的生物标记物，以在肿瘤出现之前检测出肿瘤的形成，并将其用于旨在抵消具有风险的组织中FA患者的基因组不稳定的临床试验中。微核（MN）是在后期被遗留下来的染色体片段，在子细胞中以小的附加核形式出现。在这项工作中，我们分析了40例FA患者和24例对照的脱落颊细胞中的MN频率。我们发现在FA队列中MN频率显着增加，这表明我们可以在基础条件下以及体内分裂的组织中检测FA患者的染色体脆性。因此，FA患者的脱落颊细胞中的MN测定可用于癌症风险研究和旨在鉴定癌症化学预防药物的临床试验。