Molecular Diagnosis of Burkitt's Lymphoma

TLDR

The distinction between Burkitt’s lymphoma and diffuse large‑B‑cell lymphoma is crucial because these two types of lymphoma require different treatments. The study examined whether gene‑expression profiling could reliably distinguish Burkitt’s lymphoma from diffuse large‑B‑cell lymphoma. Tumor‑biopsy specimens from 303 patients were profiled for gene expression and classified by morphology, immunohistochemistry, and t(8;14) c‑myc translocation, and a gene‑expression classifier correctly identified all 25 pathologically verified Burkitt’s lymphoma cases. Gene‑expression profiling accurately differentiated Burkitt’s lymphoma from diffuse large‑B‑cell lymphoma, revealing high c‑myc target and germinal‑center B‑cell gene expression, low MHC‑I and NF‑κB gene expression, correctly identified all 25 verified cases, flagged eight misdiagnosed cases, and showed superior overall survival with intensive chemotherapy.

Abstract

The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt's lymphoma, suggesting they represent cases of Burkitt's lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt's lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens.Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt's lymphoma from diffuse large-B-cell lymphoma.