The first broad genetic landscape map of a Burkitt lymphoma tumor has identified 70 mutations, including several not previously associated with cancer and a new one that is unique to the disease. These findings could be used to develop new drugs or aim existing therapies at mutations known to be susceptible.
Burkitt lymphoma is an aggressive form of lymphoma. This study was the first complete sequence of a Burkitt lymphoma genome, plus genes from 59 additional Burkitt cases and 94 diffuse large B cell lymphomas, which share many of the same characteristics of Burkitt lymphoma. Similarities between the malignancies can often lead to mistaken diagnoses and failed treatments.
Striking differences were found in the gene mutation pattern of Burkitt lymphomas compared with the diffuse large B cell lymphomas.
“It’s important that doctors make the right diagnosis for Burkitt lymphoma, which can be cured with the correct therapies,” said Sandeep S. Dave, MD, MBA, MS, associate professor at Duke Medicine and senior author. “But if misdiagnosed and given the standard chemotherapy regimes for diffuse large B cell lymphomas, Burkitt lymphoma patients invariably relapse.”
The analysis identified 70 genes that were frequently mutated in the Burkitt lymphomas, including a number of genes that were identified in cancer for the first time. One of the newly identified gene mutations, ID3, appeared in 34% of the Burkitt cases, but was not evident in any of the diffuse large B cell lymphomas. The mutation has a silencing effect on a gene that suppresses cell growth, enabling cells to multiply.
Dave explained that this alteration alone may not cause cancer, but when it occurs along with the MYC gene mutations that are common in Burkitt lymphoma and other malignancies, it works like an accelerant to fuel tumor growth. That finding could prove helpful for developing a new drug to function like a normal ID3 gene and suppress cancer cell proliferation in lymphomas as well as numerous other cancers.
“If we can find a way to mimic ID3, restoring the function of the gene to slow the growth of tumors, this could provide a new treatment approach,” Dave said. “We have experiments that suggest this is the case, but much more research is needed. This work provides a starting point.”
These findings were published in Nature Genetics (2012; doi:10.1038/ng.2468).