PMID- 36725383
OWN - NLM
STAT- MEDLINE
DCOM- 20230324
LR  - 20230421
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 23
IP  - 4
DP  - 2023 Apr
TI  - Whole-Exome Sequencing Revealed the Mutational Profiles of Primary Central 
      Nervous System Lymphoma.
PG  - 291-302
LID - S2152-2650(23)00015-0 [pii]
LID - 10.1016/j.clml.2023.01.003 [doi]
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a highly 
      aggressive type of extranodal non-Hodgkin lymphoma, of which approximately 90% of 
      the cases are diffuse large B-cell lymphoma (DLBCL). In recent years, the 
      incidence of PCNSL has significantly increased in women and older men. Although 
      advanced treatments such as high-dose methotrexate (HD-MTX) and targeted agents 
      have been introduced, the prognosis of these patients remains poorer than those 
      with other forms of non-Hodgkin's lymphoma. METHODS: Twelve cases of Chinese 
      PCNSL were analyzed to detect their genetic alterations using whole-exome 
      sequencing (WES). We identified 448 potential somatic single nucleotide variants 
      (SNVs) with a median of 12 SNVs per PCNSL sample and 35 small indels with 
      potentially protein-changing features in 9 PCNSL samples. RESULTS: We found that 
      myeloid differentiation factor 88 (MYD88) had the highest mutation frequency, 
      which affected the activity of the nuclear factor-kappaB (NF-kappaB) pathway. PCNSL 
      samples with low-density lipoprotein receptor-related protein 1B (LRP1B) 
      mutations had a higher mutation rate than samples with wild-type LRP1B. 
      Polycystic kidney and hepatic disease 1 (PKHD1), the causal gene of autosomal 
      recessive polycystic kidney disease (ARPKD), was identified in 2 PCNSL cases and 
      exhibited missense mutations. Pathway analysis revealed enrichment in pathways 
      associated with central carbon metabolism in cancer, renal cell carcinoma, 
      nicotine addiction, bladder cancer, and long-term depression. CONCLUSIONS: WES 
      revealed significantly mutated genes associated with the molecular mechanisms of 
      PCNSL, which could serve as therapeutic targets to improve patient outcomes.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Zhang, Rui
AU  - Zhang R
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Wei, Boyuan
AU  - Wei B
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Hu, Yiyang
AU  - Hu Y
AD  - Department of Medical Genetics and Developmental Biology, Fourth Military Medical 
      University, Xi'an, China.
FAU - Lv, Wenying
AU  - Lv W
AD  - Department of Neurosurgery, the Sixth Medical Centre, Chinese PLA General 
      Hospital, Beijing,China.
FAU - Adilai, Abudurexiti
AU  - Adilai A
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Yang, Fan
AU  - Yang F
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Zhang, Jianning
AU  - Zhang J
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China. Electronic address: jnzhang2018@163.com.
FAU - Cheng, Gang
AU  - Cheng G
AD  - Department of Neurosurgery, the First Medical Centre, Chinese PLA General 
      Hospital, Beijing, China. Electronic address: yjscg2003@126.com.
LA  - eng
PT  - Journal Article
DEP - 20230112
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
SB  - IM
MH  - Male
MH  - Humans
MH  - Female
MH  - Aged
MH  - Exome Sequencing
MH  - *Central Nervous System Neoplasms/genetics/pathology
MH  - Mutation
MH  - *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics/metabolism
MH  - Central Nervous System/pathology
OTO - NOTNLM
OT  - Genetic alteration
OT  - High-dose methotrexate
OT  - Interaction network
OT  - MYD88
OT  - Pathway analysis
COIS- Disclosures The authors have no relevant financial or non-financial interests to 
      disclose.
EDAT- 2023/02/02 06:00
MHDA- 2023/03/25 06:00
CRDT- 2023/02/01 21:59
PHST- 2022/10/21 00:00 [received]
PHST- 2022/12/31 00:00 [revised]
PHST- 2023/01/08 00:00 [accepted]
PHST- 2023/02/02 06:00 [pubmed]
PHST- 2023/03/25 06:00 [medline]
PHST- 2023/02/01 21:59 [entrez]
AID - S2152-2650(23)00015-0 [pii]
AID - 10.1016/j.clml.2023.01.003 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2023 Apr;23(4):291-302. doi: 
      10.1016/j.clml.2023.01.003. Epub 2023 Jan 12.