Department of Neurology, Yale School of Medicine, New Haven, USA.
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Br J Haematol. 2021 Apr;193(2):375-379. doi: 10.1111/bjh.17319. Epub 2021 Jan 22.
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.
SLIT2 是一个已知的肿瘤抑制基因，但其在原发性中枢神经系统淋巴瘤（PCNSL）的发病机制中尚未被涉及。对 6 名未经治疗的 PCNSL 患者的配对血液和肿瘤 DNA 样本进行外显子组测序，我们发现了新的 SLIT2 变异（p.N63S、p.T590M、p.T732S），这些变异与我们队列中的无进展生存期较短以及 cBio Cancer Genomics Portal 中来自淋巴恶性肿瘤的大型验证队列中的总生存期较短相关。WNT 和 NF-κB 报告基因荧光素酶检测表明，检测到的改变是功能丧失变异。鉴于其可能的预后意义，SLIT2 在 PCNSL 发病机制和进展中的作用值得进一步研究。
