Poster Presentation 39th Annual Lorne Genome Conference 2018

Mutation Analysis and Effect on Prognosis of Direct Antiglobulin Test Positivity in Diffuse Large B-Cell Lymphoma (#130)

Caitlin Coombes 1 2 , Joshua Tobin 3 4 , Kartik Saxena 2 , Jun Hee Lim 5 , Bruce Shadbolt 6 , Yogesh Jeelall 7 8 , Chris Goodnow 7 9 , Thomas D Andrews 7 , Sanjiv Jain 10 , Simon Jiang 7 11 , Keisuke Horikawa 5 , Dipti Talaulikar 2 5
  1. Australian National University, Acton, ACT, Australia
  2. Haematology Translational Research Unit, Haematology Department, The Canberra Hospital, Garran, ACT, Australia
  3. Princess Alexandra Hospital, Brisbane, QLD, Australia
  4. Diamantina Institute, University of Queensland, Brisbane, QLD, Australia
  5. Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia
  6. Centre for Advances in Epidemiology and IT, The Canberra Hospital, Garran, ACT, Australia
  7. Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia
  8. School of Medicine and Pharmacology, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia
  9. Department of Immunology , Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  10. Anatomical Pathology Department, The Canberra Hospital, Garran, ACT, Australia
  11. Renal Medicine Department, The Canberra Hospital, Garran, ACT, Australia

Introduction

Direct Antiglobulin Test (DAT) positivity occurs at higher rates in patients with Non-Hodgkin Lymphoma. This study examined the genetic differences between DAT positive (DAT +) and DAT negative (DAT-) DLBCL cases, and the effect of DAT positivity on survival and revised international prognostic index (R-IPI) in Diffuse Large B-Cell Lymphoma (DLBCL).

 

Method

One hundred and thirteen cases that had undergone DAT testing at the time of DLBCL diagnosis were included. DNA was extracted from 7 DAT+ and 8 DAT- patient samples and targeted next-generation sequencing (NGS) was performed. Analysis of survival outcomes was assessed by the Kaplan-Meier method and Cox proportional hazards regression.

 

Results

An average of 10.07 mutations per DLBCL clone were found on NGS (DAT+ 10.14 vs DAT-10.00). Mutations were found in genes and B-cell pathways associated with oncogenesis and autoimmunity in both DAT+ and DAT- groups. The most recurrently mutated genes were KMT2D (n=13), MYOM2 (n=9), and EP300 (n=8), which were all mutated in both groups. The genes associated with the non-canonical NFκB pathway were found to be more frequently mutated in the DAT+ group, with 6 mutations in the DAT+ group compared with 1 mutation found in the DAT- group.

There was a non-significant difference in overall survival between the DAT+ and DAT- groups (p=0.19). DAT significantly influenced the effect of R-IPI on survival (p=0.017). Within the DAT- group, R-IPI maintained its strong predictive power for overall survival (p<0.0001). Within the DAT+ group, the two represented R-IPI groups were not significantly different in their overall survival (p=0.74).

 

Conclusion

Both DAT positive and DAT negative patient groups showed high rates of non-synonymous mutations in genes that are frequently targeted in DLBCL. This study did not demonstrate a significant effect on survival of DAT positivity in patients with DLBCL, but a moderating influence on R-IPI’s survival effect.