Molecular genetics of childhood, adolescent and young adult non‐Hodgkin lymphoma

Abstract

Summary Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future.

Personal tumor antigens in blood malignancies: genomics-directed identification and targeting

“…Gene fusions have the potential to give rise to immunogenic neoepitopes, as has been recently demonstrated in head and neck cancers (79). Gene fusions often arise from chromosomal translocations and are a hallmark of hematological malignancies (51,(80)(81)(82)(83). Although immunogenic neoantigens arising from gene fusions have long been described in hematological neoplasms (45,(84)(85)(86), only BCR-ABL has been targeted therapeutically using vaccination approaches, which were able to induce specific T cell responses (87)(88)(89)(90).…”

Application of 2016 WHO classification in the diagnosis of paediatric high-gradeMYC-negative mature B-cell lymphoma with Burkitt-like morphological features

“…If MYC rearrangement is present, the diagnosis will be BL unless the morphology or phenotype is significantly atypical, then testing for BCL2 and BCL6 may be necessary to rule out double-hit/triple-hit lymphoma. If it is MYC -negative, based on our results and the published data,7–12 four possibilities should be considered. The first consideration should always be BLL-11q, which seems under-recognised.…”

“…HGBCLs, NOS, include cases with atypical BL features or blastoid morphology without double-hit or triple-hit cytogenetic findings, regardless of MYC status. This category seems not applicable for paediatric cases, considering the excellent prognosis of most paediatric high-grade B-cell non-Hodgkin's lymphoma cases and their distinct molecular features 7–12…”

Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin’s lymphoma patients

“…The diagnosis and classification of NHL continue to be based on morphology and immunophenotype, and specific genetic changes are not taken into account in the definition of lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL are associated with prognosis or represent potential therapeutic targets, thus there exists an emerging role for marker testing to help predict outcomes and guide therapy (Miles et al, 2016). Approximately half of A-NHL patients cannot be cured using standard treatment (Alici et al, 2003); therefore, the identification of new markers of treatment response and outcome is of some importance.…”