In:
Neuropathology and Applied Neurobiology, Wiley, Vol. 42, No. 3 ( 2016-04), p. 279-290
Abstract:
Primary central nervous system lymphoma ( PCNSL ) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor‐κ B ( NF ‐κ B ) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF ‐κ B pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL . Methods We conducted the systematic sequencing of 21 genes relevant to the NF ‐κ B signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas ( GBMs ) for validation. Results The results showed that 68 out of 71 PCNSLs had mutations in the NF ‐κ B gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88 , frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265 . Conclusions The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B ‐cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system ( CNS ) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.
Type of Medium:
Online Resource
ISSN:
0305-1846
,
1365-2990
DOI:
10.1111/nan.2016.42.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2008293-9
