ABSTRACT
Background and aims: There is an increased risk of lymphomas in inborn errors of immunity (IEI); however, germline genetic testing is rarely used in oncological patients, even in those with early onset of cancer. Our study focuses on a child with a recombination-activating gene 1 (RAG1) deficiency who was identified through a screening program for Slavic founder genetic variants among patients who died with malignancy at an early age in Belarus. Results: We identified one homozygous founder RAG1 variant out of 24 available DNA samples from 71 patients who developed lymphoma aged <3 years from the Belarusian cancer registry between 1986 and 2023. Our patient had an episode of pneumonia at 3â months of age and was hospitalized for respiratory distress, candida-positive lung disease, and lymphadenopathy at 14 months of age. The diagnosis of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) was established. The patient had a normal lymphocyte count that decreased over time. One month after chemotherapy initiation, the patient died due to sepsis and multiple organ failure without a genetic diagnosis. In a retrospective analysis, T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) were undetectable in peripheral blood. Conclusions: A targeted screening program designed to detect a Slavic founder variant in the RAG1 gene among children revealed a 14-month-old Belarusian male infant with low TREC levels who died of EBV-driven DLBCL and complications of chemotherapy including infections. This case highlights how patients with IEI and recurrent infections may develop serious non-infectious complications, such as fatal malignancy. It also emphasizes the importance of early identification, such as newborn screening for severe combined immune deficiency. Earlier diagnosis of RAG deficiency could have prompted hematopoietic stem cell transplant well before the DLBCL occurrence. This likely would impact the onset and/or management strategies for the cancer.
ABSTRACT
Background/Aim: The prognosis of high-risk and relapsed neuroblastoma (NB) patients remains poor. The identification of tumor-associated markers is important for differential diagnosis, prognosis, and the development of targeted therapies. The aim of the study was to determine the expression profile of nine most common NB antigens and assess their association with clinicopathological characteristics and patient survival. Patients and Methods: Tumor samples from 86 patients with NB were evaluated for the expression of tumor-associated antigen (TAA) using quantitative PCR. Twenty-one patients with benign tumors and 17 healthy donors were assigned as controls. Results: Overexpression of tyrosine hydroxylase (TH), PHOX2B, PRAME, GPC2, B7-H3, and Survivin is the most typical for NB. Positive expression of MAGEA3, MAGEA1, and NY-ESO-1 at low levels was detected in 54%, 48%, and 52%, respectively, and was not NB specific. Higher TH expression was observed in samples without MYCN-amplification, while higher expression of Survivin, PHOX2B, and GPC2 was significantly associated with the presence of 1p.36 deletion. Overexpression of TH, PHOX2B, and MAGEA1 was associated with better event-free (EFS) and overall survival (OS). Survivin overexpression was associated with poor EFS but had no impact on OS. Multivariate analysis confirmed Survivin as independent marker for poor survival, and PHOX2B and MAGEA1 for better survival. Conclusion: High expression of TH, PHOX2B, and MAGEA1 genes are favorable prognostic factors for OS and EFS, whereas high expression of Survivin is associated with an increased risk of relapse or progression.
