Instruct: Identify the main category of Medrxiv papers based on the titles and abstracts
Query: Genetic Subgroups Inform on Pathobiology in Adult and Pediatric Burkitt Lymphoma Burkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas (NHL) and is relatively rare but significantly more lethal when diagnosed in adults. The global incidence is highest in Sub-Saharan Africa, where Epstein-Barr virus (EBV) positivity is observed in 95% of all tumors. Both pediatric (pBL) and adult (aBL) cases are known to share some driver mutations, for example MYC translocations, which are seen in > 90% of cases. Sequencing efforts have identified many common somatic alterations that cooperate with MYC in lymphomagenesis with approximately 30 significantly mutated genes (SMG) reported thus far. Recent analyses revealed non-coding mutation patterns in pBL that were attributed to aberrant somatic hypermutation (aSHM). We sought to identify genomic and molecular features that may explain clinical disparities within and between aBL and pBL in an effort to delineate BL subtypes that may allow for the stratification of patients with shared pathobiology. Through comprehensive sequencing of BL genomes, we found additional SMGs, including more genetic features that associate with tumor EBV status, and established three new genetic subgroups that span pBL and aBL. Direct comparisons between pBL and aBL revealed only marginal differences and the mutational profiles were consistently better explained by EBV status. Using an unsupervised clustering approach to identify subgroupings within BL and diffuse large B-cell lymphoma (DLBCL), we have defined three genetic subgroups that predominantly comprise BL tumors. Akin to the recently defined DLBCL subgroups, each BL subgroup is characterized by combinations of common driver mutations and non-coding mutations caused by aSHM. Two of these subgroups and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among the aBL and pBL cohorts. These findings highlight not only a shared pathogenesis between aBL and pBL, but also establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiological studies, and diagnostic and therapeutic strategies.
53
The categories of this paper are: pathology
25
The categories of this paper are: improvement
33
The categories of this paper are: physical
9
The categories of this paper are: diseases
29
The categories of this paper are: anesthesia
37
The categories of this paper are: aids
59
The categories of this paper are: respiratory
52
The categories of this paper are: nursing
38
The categories of this paper are: hiv
20
The categories of this paper are: psychiatry
64
The categories of this paper are: ophthalmology
34
The categories of this paper are: therapy
50
The categories of this paper are: medical
4
The categories of this paper are: reproductive
35
The categories of this paper are: pediatrics
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The categories of this paper are: allergy