FANCA, TP53, and del(5q)/RPS14 alterations in a patient with T-cell non-Hodgkin lymphoma and concomitant Fanconi anemia and Li-Fraumeni syndrome

Edoardo Errichiello; Tommaso Mina; Patrizia Morbini; Marco Zecca; Orsetta Zuffardi

doi:10.1016/j.cancergen.2020.10.003

FANCA, TP53, and del(5q)/RPS14 alterations in a patient with T-cell non-Hodgkin lymphoma and concomitant Fanconi anemia and Li-Fraumeni syndrome

Cancer Genet. 2021 Aug:256-257:179-183. doi: 10.1016/j.cancergen.2020.10.003. Epub 2020 Oct 31.

Authors

Edoardo Errichiello¹, Tommaso Mina², Patrizia Morbini³, Marco Zecca², Orsetta Zuffardi⁴

Affiliations

¹ Medical Genetics Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy. Electronic address: edoardo.errichiello@unipv.it.
² Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
³ Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
⁴ Medical Genetics Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy.

PMID: 33183999
DOI: 10.1016/j.cancergen.2020.10.003

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.

Keywords: FANCA; Fanconi anemia (FA); Li-Fraumeni syndrome (LFS); T-cell non-Hodgkin lymphoma (NHL); TP53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Child, Preschool
Fanconi Anemia / complications
Fanconi Anemia / immunology*
Fanconi Anemia Complementation Group A Protein / genetics*
Gene Deletion*
Humans
Li-Fraumeni Syndrome / complications
Li-Fraumeni Syndrome / immunology*
Loss of Heterozygosity / genetics
Lymphoma, Non-Hodgkin / complications
Lymphoma, Non-Hodgkin / immunology*
Ribosomal Proteins / genetics*
T-Lymphocytes / immunology*
Tumor Suppressor Protein p53 / genetics*

Substances

FANCA protein, human
Fanconi Anemia Complementation Group A Protein
RPS14 protein, human
Ribosomal Proteins
Tumor Suppressor Protein p53