We traced the neoplastic history (from 5 to 11 years of age) of a child with concomitant Fanconi anemia and Li-Fraumeni syndrome. Interestingly, the patient developed a highly malignant T-cell non-Hodgkin lymphoma (NHL), which does not represent the typical tumor type in the two aforementioned syndromes, presumably due to the underlying genomic instability.

By using a combination of molecular and immunohistochemical approaches, we characterized the accumulation of multiple genetic alterations in a single patient, with both germline (parentally inherited biallelic FANCA variants and a likely de novo nonsense variant in TP53) and somatic (TP53 loss of heterozygosity and 5q interstitial deletion) contributions. Our findings support the interplay of TP53 and FANC genes in DNA damage response pathways and further highlight the genetic heterogeneity of lymphomas as well as the contribution of genomic instability to lymphomagenesis.

我们追踪了一名患有范可尼贫血症和 Li-Fraumeni 综合征的儿童的肿瘤病史（从 5 岁到 11 岁）。有趣的是，患者发展为高度恶性的 T 细胞非霍奇金淋巴瘤 (NHL)，这并不代表上述两种综合征中的典型肿瘤类型，可能是由于潜在的基因组不稳定性。

通过使用分子和免疫组织化学方法的组合，我们表征了单个患者中多种遗传改变的积累，包括种系（亲本遗传的双等位基因FANCA变异和TP53 中可能的de novo nonsense 变异）和体细胞（TP53杂合性缺失和5q 间隙删除）贡献。我们的研究结果支持TP53和FANC基因在 DNA 损伤反应途径中的相互作用，并进一步强调了淋巴瘤的遗传异质性以及基因组不稳定性对淋巴瘤发生的贡献。