1. FANCA, TP53, and del(5q)/RPS14 alterations in a patient with T-cell non-Hodgkin lymphoma and concomitant Fanconi anemia and Li-Fraumeni syndrome
- Author
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Patrizia Morbini, Edoardo Errichiello, Marco Zecca, Orsetta Zuffardi, and Tommaso Mina
- Subjects
Genome instability ,Ribosomal Proteins ,Cancer Research ,T-Lymphocytes ,Loss of Heterozygosity ,Biology ,Loss of heterozygosity ,Li-Fraumeni Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Fanconi anemia ,hemic and lymphatic diseases ,Genetics ,medicine ,Humans ,Molecular Biology ,Base Sequence ,Fanconi Anemia Complementation Group A Protein ,Genetic heterogeneity ,Lymphoma, Non-Hodgkin ,medicine.disease ,FANCA ,Lymphoma ,T-Cell Non-Hodgkin Lymphoma ,Fanconi Anemia ,Li–Fraumeni syndrome ,030220 oncology & carcinogenesis ,Child, Preschool ,Cancer research ,Tumor Suppressor Protein p53 ,Gene Deletion - Abstract
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.
- Published
- 2019