Distinct genetic alterations in CD10-negative MUM1-positive follicular lymphoma.

in Pathology by Yan Yang, Wei Wang, Liang Zhang, Xu Lu, Huihui Li, Yixiong Liu, Zhouyi Xu, Danhui Zhao, Jia Chai, Longfei Shao, Linni Fan, Mingyang Li, Yanru Yang, Chuanshu Gao, Haibo Wu, Zhe Wang

TLDR

  • CD10-MUM1+ FL is a distinct subtype of conventional FL with unique clinical, pathological, and genetic features, which may require tailored therapeutic approaches.

Abstract

Conventional follicular lymphoma (FL) is positive for CD10 and negative for multiple myeloma oncogene 1 (MUM1). However, a subset of FL shows CD10-MUM1+ features, and the genetic alterations of this unique FL subtype are poorly understood. Thus, we conducted whole-exome sequencing in 20 cases of CD10-MUM1+ FL and analysed the genetic and clinicopathological features of these patients. The results suggested that CD10-MUM1+ FL patients were predominantly elderly women, lacked BCL2 rearrangement (17/17, 100%) ​and showed a higher grade (17/20, 85% grade 3) than patients with conventional FL. The most frequently mutated genes in these tumours were CD79B, GOLGA6L2, IGLL5, KMT2D, NFKBIE, ROBO1, BTG2, DTX1, LRP3 and PTPN6. In contrast to conventional FL, CD10-MUM1+ FL exhibited an elevated mutation frequency of CD79B and NFKBIE and decreased mutation frequencies of CREBBP, BCL2, KMT2D and TNFRSF14. No significant difference was found in the overall survival between CD10-MUM1+ FL and conventional FL patients. In summary, this study demonstrated that CD10-MUM1+ FL has unique clinical, pathological ​and genetic features.

Overview

  • The study focused on whole-exome sequencing of 20 cases of CD10-MUM1+ conventional follicular lymphoma (FL) to understand their genetic alterations.
  • The study included predominantly elderly women with a higher grade (85%) and lacked BCL2 rearrangement (100%) compared to conventional FL.
  • The primary objective was to identify the genetic features that distinguish CD10-MUM1+ FL from conventional FL.

Comparative Analysis & Findings

  • The study found that CD10-MUM1+ FL patients had a higher mutation frequency of CD79B and NFKBIE and lower mutation frequencies of CREBBP, BCL2, KMT2D, and TNFRSF14 compared to conventional FL.
  • Although the overall survival was not significantly different between CD10-MUM1+ FL and conventional FL, the genetic features of CD10-MUM1+ FL were distinct from those of conventional FL.
  • The most frequently mutated genes in CD10-MUM1+ FL were CD79B, GOLGA6L2, IGLL5, KMT2D, NFKBIE, ROBO1, BTG2, DTX1, LRP3, and PTPN6.

Implications and Future Directions

  • The findings of this study provide insight into the genetic features of CD10-MUM1+ FL, which may inform the development of targeted therapeutic strategies.
  • Future studies could investigate the biological and clinical significance of the genetic alterations identified in CD10-MUM1+ FL.
  • The study's results also highlight the need for further research into the molecular mechanisms underlying the development and progression of CD10-MUM1+ FL.
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