ABSTRACT
Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.
Subject(s)
Humans , DNA Copy Number Variations , Nuclear Proteins/genetics , Central Nervous System Neoplasms/pathology , Transcription Factors/genetics , Prognosis , Lymphoma/genetics , Genomics , China , Central Nervous System/pathology , Bromodomain Containing Proteins , Cell Cycle Proteins/geneticsABSTRACT
Objective To investigate the predictive value of class Ⅲ β-tubulin protein expression in tumor tissue for the efficacy of taxol combined chemotherapy in stage Ⅲ s/Ⅳ gastric carcinoma patients.Methods Tumor biopsy samples were obtained and class Ⅲ β-tubulin protein expression were examined by immunohistochemical staining before chemotherapy.According to different expression of class Ⅲ β-tubulin,the patients were divided into two groups,group A(low expression of class Ⅲ β-tubulin),group B(high expression of class Ⅲ β-tubulin).The patients were assigned to be received 4 to 6 cycles of Taxol and S-1 chemotherapy regimens and followed up until death or lost.Response rate(RR),overall survival(OS)and time to tumor progression(TTP)were assessed.Results There was no significant difference in clinical characteristics among patients with different expression rate.The RR was higher and TIP was longer in group A than in group B(53.3 ％ vs 36.7 ％,198 days vs 146 days,P ＜ 0.05 respectively),and no significant differences of OS in two groups(P ＞ 0.05).Conclusion The expression level of class Ⅲ β-tubulin in tumor tissue is probably a predictor for the efficacy of taxol in gastric cancer patients,taxol combined chemotherapy is more suitable for patients with lower expression of class Ⅲ β-tubulin.
ABSTRACT
The taxol s effect of inducing apoptosis is mainly related to its ability to promote tubulin polymerization and prevent tubulin chain depolarization. Drug resistance is the main restriction factor for clinical usage of taxol. Some basic and clinical studies support that poor response to taxol and poor prognosis are related to overexpression of β tubulin Ⅲ.