The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to results of an abstract from the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, whole exome and transcriptome sequencing of a large number of cases of follicular lymphoma revealed “a high degree of genetic heterogeneity” in this disease. 

Follicular lymphoma is an incurable, indolent B-cell lymphoma with a highly variable clinical course. Although follicular lymphoma is frequently characterized by translocation, and subsequent upregulation, of the BCL2 gene, this genomic alteration is not sufficient to induce B-cell transformation in this disease. Rather, the process of tumorigenesis in follicular lymphoma is believed to also involve other molecular abnormalities. 

However, at the present time, the genomic/transcriptomic landscape of follicular lymphoma with respect to potential oncogenic cooperation/interaction of molecular alterations and the impact of these associations on clinical outcome has not been well characterized. 

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In this study, DNA and RNA sequencing was performed on paired normal and tumor specimens collected from 1042 patients with newly diagnosed follicular lymphoma using a large panel covering 110 mega base pairs (Mbp), including approximately 40 Mbp and 70 Mbp corresponding to exonic and non-exonic regions, respectively. Coverage included the immunoglobulin, T-cell receptor, and CD3 loci, likely breakpoint regions, long noncoding RNAs and microRNAs relevant to lymphoma, as well as the genomes of 8 viruses (eg, HIV, Epstein-Barr virus) that have been implicated in the development of cancer. 


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Key findings from the genomic analyses were at least 1 mutation in a chromatin-modifying gene in 100% of cases. The most commonly identified mutations occurred in KMT2D, BCL2, IGLL5, and CREBBP, although mutations occurring in SPEN, BIRC6 and SETD2 were also found. 

Notably, 100 different gene mutations, each with a frequency of 2% or higher, were identified in this patient cohort, the authors reported in the abstract.

RNA and DNA sequencing analyses showed that the previously identified immune response 2 signature, which has been associated with poor clinical outcome in follicular lymphoma, was correlated with the presence of mutations in the BIRC6 gene. Other findings included an association between grade 3 disease and a cluster of alterations in BCL6 and TP53.

Findings from a corresponding study of over 1000 cases of diffuse large B-cell lymphoma demonstrated a “continuum of highly overlapping genetic alterations” in comparison with follicular lymphoma suggestive of similar underlying pathogenetic processes in these 2 diseases.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.

Reference

LiX,  KositskyR,  Reddy A, et al. Whole exome and transcriptome sequencing in 1042 cases reveals distinct clinically relevant genetic subgroups of follicular lymphoma. Blood. 2019; 134(Supplement 1):Abstract 19. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.