ORLANDO – Researchers have identified novel recurrently mutated genes and pathways in follicular lymphoma, including common mutations in genes that play a role in amino acid signaling to mTOR and pre-B-cell receptor signaling, a study presented at the 57th American Society of Hematology (ASH) Annual Meeting & Exposition has shown.1
Follicular lymphoma is the second most common form of non-Hodgkin’s lymphoma in the United States. “It is still not curable with chemotherapy,” said Sami N. Malek, associate professor of hematology at the University of Michigan in Ann Arbor, MI, during his presentation.
Although previous evidence has demonstrated that follicular lymphoma carries numerous recurrently mutated genes, knowledge regarding the coding genome in follicular lymphoma remains limited.
Therefore, researchers sought to use paired-end massively parallel sequencing of 54 follicular lymphoma cases in order to “identify the full complement of mutated genes in follicular lymphoma,” Dr Malek said.
Results showed heterozygous missense mutations in the mTOR regulator RRAGC, which facilitates recruitment of mTOR through the raptor subunit to lysosomal membranes, in 10% of follicular lymphoma cases.
Researchers also identified additional mutations in other mTOR components associated with lysosomal amino acid sensing, including recurrent mutations in the v-ATPase subunit ASP6V1B2 and the accessory subunit ATP6VAP1.
Furthermore, researchers discovered a high frequency of mutations in the surrogate light chain gene IGLL5 in follicular lymphoma, a vital part of the pre-B-cell receptor, which suggests that IGLL5 plays a role in the pathogenesis of follicular lymphoma.
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The findings ultimately help to better understand the genetic basis of follicular lymphoma and provide potential therapeutic specific pathway targets in follicular lymphoma.
“The question is: Are novel follicular lymphoma mutations affecting the response to ibrutinib or idealisib?” Dr Malek concluded.
- Malek SN, Bernard D, Ying ZX, et al. Analysis of 54 follicular lymphomas by whole exome sequencing identifies multiple novel recurrently mutated pathways. Oral presentation at; 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.