Sylvester Researchers Gain New Insights into Rare Lymphoma

Genomic sequencing data may provide therapeutic targets for drug developers.

Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have conducted a comprehensive genomic analysis of tumor samples from patients with a rare cancer known as ocular adnexa marginal zone lymphoma (OAMZL). The sequences revealed several unique gene mutations not found in other marginal zone lymphomas.

These results highlight the importance of precisely characterizing OAMZL patients, as well as identifying several mutated genes that could be used as therapeutic targets. The study was published in Cancer Research Communications. 

“By doing this large-scale sequencing and copy number analyses, we identified multiple new mutations and genetic variations that previously were not reported in this disease,” said Izidore S. Lossos, M.D., chief, lymphoma Section, director of the lymphoma program, and senior author of the paper. “We have now established a genetic landscape underlying this disease.”

Extranodal marginal zone lymphomas are relatively rare cancers that can affect the stomach, skin, and other areas. OAMZL is one of the less common forms, affecting areas around the eyes, though usually not inside the eye.

While most oncologists may never see a single case, Bascom Palmer Eye Institute draws OAMZL patients from throughout the United States and other countries, giving Dr. Lossos and other Sylvester researchers ample patient samples to study. In this case, the team sequenced the exomes (DNA sequences that code for genes) from 69 OAMZL patients.

The study confirmed two well-known cancer signaling pathways: the B-cell receptor (BCR) and NFkB. In addition, the analysis found previously unseen mutations in multiple genes in both pathways. The study also identified novel mutations in other pathways including NOTCH and NFAT, neither of which had been previously implicated in OAMZL (though NOTCH mutations had been detected in other marginal cell lymphomas).

The discovery of these mutations could potentially lead to new targeted therapies. In addition, it reveals that OAMZL has unique genetic aberrations that were not previously reported in extranodal marginal zone lymphomas originating in other locations.

“What we can learn from this genetic landscape is that, in contrast to other marginal cell lymphomas in other locations that were analyzed previously, the mutational path is quite different,” said Dr. Lossos.

These mutational signatures may reflect the many driving mechanisms associated with different marginal cell lymphomas. In some cases, genetic OAMZL mutations attributed to UV radiation were seen in Florida patients, possibly stemming from excessive UV exposure that might contribute to tumor pathogenesis.

On a clinical level, identifying so many novel mutations could lead to better therapies. Just as importantly, the study underscores the fact that extranodal marginal zone lymphomas are not one disease and differ by anatomic locations. Clinicians must do everything possible to identify the traits in each patient’s lymphoma.

“These different causes may activate the same signaling pathways, but they do it through various mechanisms,” said Dr. Lossos. “We need to perform some analysis on each patient with this lymphoma to understand which mechanisms are driving their underlying disease.”

Tags: Bascom Palmer Eye Institute, Dr. Izidore Lossos, lymphoma, Sylvester Comprehensive Cancer Center