Abstract Details

Title Whole Exome Sequencing Identifies Novel SLIT2 Mutations in Primary CNS Lymphoma

Topic Neuro-oncology

Presentation(s) S14 - Neuro-oncology (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Objective With this study we aimed to better understand the genetic landscape of primary CNS lymphoma (PCNSL) and its clinical implications. We specifically focused on previously undescribed mutations.

Background Whole exome sequencing (WES) data on PCNSL is scarce and correlation with clinical observations is needed to facilitate personalized care. Here we present WES data of six PCNSL and correlated findings with clinical outcome.

Design/Methods WES was performed on paired blood and tumor DNA samples from six PCNSL patients to a median coverage of 100x (range: 73-135x) and 194x (range: 127-232x), respectively. Selected, novel mutations were validated with Sanger sequencing. Epstein-Barr virus (EBV) status was assessed in tumor tissue. Progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. P values < 0.05 were considered significant.

Results We found a median of 22 (range: 11-68) somatic copy number variations, 171 (range: 73-276) somatic single-nucleotide variants and 11 (range: 0-22) somatic insertions/deletions per PCNSL. CDKN2A loss, identified in five samples, was the most commonly detected copy number alteration. All five EBV-negative PCNSL carried mutations, in previously described PIM1, MYD88, CD79B or BTG genes. No previously reported mutations were found in the EBV-positive tumor. In three PCNSL, we identified novel SLIT2 mutations (p.N63S, p.T586M, p.T728S) clustered around the leucine-rich repeats (LRR) domains. SLIT2 mutations were associated with significantly shorter PFS in our cohort (p = 0.036).

Conclusions

PCNSL harbored previously unknown SLIT2 mutations clustered around domains that interact with ROBO proteins and are critical for signaling. SLIT2 mutations may be predictive of less favorable outcome in PCNSL. Additional clinical and molecular evaluation of these mutations is warranted.

Authors/Disclosures
Leon D. Kaulen, MD PRESENTER	Dr. Kaulen has nothing to disclose.
	No disclosure on file
	No disclosure on file
Philipp Karschnia	Philipp Karschnia has nothing to disclose.
	No disclosure on file
	No disclosure on file
Joachim M. Baehring, MD, FAAN (Yale University School of Medicine)	Dr. Baehring has nothing to disclose.

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