Exome sequencing identifies SLIT2 variants in primary CNS lymphoma

Br J Haematol. 2021 Apr;193(2):375-379. doi: 10.1111/bjh.17319. Epub 2021 Jan 22.

Abstract

SLIT2 constitutes a known tumour suppressor gene, which has not yet been implicated in the pathogenesis of primary central nervous system lymphoma (PCNSL). Performing exome sequencing on paired blood and tumour DNA samples from six treatment-naïve PCNSL patients, we identified novel SLIT2 variants (p.N63S, p.T590M, p.T732S) that were associated with shorter progression-free survival in our cohort and shorter overall survival in a large validation cohort of lymphoid malignancies from the cBio Cancer Genomics Portal. WNT- and NF-κB-reporter luciferase assays suggest detected alterations are loss-of-function variants. Given the possible prognostic implications, the role of SLIT2 in PCNSL pathogenesis and progression warrants further investigation.

Keywords: CNS lymphoma; Epstein-Barr virus; SLIT2; exome sequencing; genetics; prognosis.

MeSH terms

  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / virology
  • Cohort Studies
  • Exome Sequencing / methods*
  • Female
  • Genomic Structural Variation / genetics
  • Genomics / methods
  • Herpesvirus 4, Human / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphoma, Non-Hodgkin / diagnosis
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • NF-kappa B / genetics
  • Nerve Tissue Proteins / genetics*
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies

Substances

  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nerve Tissue Proteins
  • Slit homolog 2 protein