scholarly journals Systematic identification of mutations and copy number alterations associated with cancer patient prognosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Joan C Smith ◽  
Jason M Sheltzer
Keyword(s):  
Copy Number ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Driver Genes ◽  
Cancer Driver ◽  
Molecular Alterations ◽  
Patient Prognosis ◽  
Almost All ◽  
Systematic Identification

Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almost all cancer driver genes contain remarkably little information on patient prognosis. However, CNAs in these same driver genes harbor significant prognostic power. Focal CNAs are associated with worse outcomes than broad alterations, and CNAs in many driver genes remain prognostic when controlling for stage, grade, TP53 status, and total aneuploidy. By performing a meta-analysis across independent patient cohorts, we identify robust prognostic biomarkers in specific cancer types, and we demonstrate that a subset of these alterations also confer specific therapeutic vulnerabilities. In total, our analysis establishes a comprehensive resource for cancer biomarker identification and underscores the importance of gene copy number profiling in assessing clinical risk.

scholarly journals MET Gene Copy Number Predicts Worse Overall Survival in Patients with Non-Small Cell Lung Cancer (NSCLC); A Systematic Review and Meta-Analysis

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107677 ◽  
Author(s):  
Anastasios Dimou ◽  
Lemuel Non ◽  
Young Kwang Chae ◽  
William J. Tester ◽  
Konstantinos N. Syrigos
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung

scholarly journals MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lun-Xi Peng ◽  
Guang-Ling Jie ◽  
An-Na Li ◽  
Si-Yang Liu ◽  
Hao Sun ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Precision Oncology ◽  
Next Generation ◽  
Driver Genes ◽  
Generation Sequencing

Abstract Background MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for MET amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in MET amplification remains uncertain. Methods Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment. MET amplification by FISH was defined as a MET/CEP7 ratio of  >  2.0 and/or copy number (CN)  >  5. MET amplification by NGS was defined as gene copy number (GCN)  ≥  5. Results The concordance rate among FISH and NGS was 62.5% (25/40). MET amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with MET amplification) vs. 6.7% (1/15 without MET amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P  < 0.001). MET amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with MET GCN  ≥ 5) vs. 40.0% (12/30, with MET GCN  < 5); the median PFS was 4.8 months vs. 2.2 months (P  = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS. Conclusions MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.

scholarly journals Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Li ◽  
Jun Zhang ◽  
Dan Liao ◽  
Lu Yang ◽  
Yingxiong Wang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Meta Analysis ◽  
Significant Risk ◽  
Gene Copy Number ◽  
Significant Risk Factor ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Case Control Studies

Abstract Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE.

The prognostic impact of high MET gene copy number on non-small cell lung cancer: A meta-analysis of eight studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22049-e22049
Author(s):  
Anastasios Dimou ◽  
Lemuel Non ◽  
Kostas N Syrigos
Keyword(s):  
Lung Cancer ◽  
Primary Tumor ◽  
Copy Number ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Prognostic Impact ◽  
Fixed Effects Model ◽  
Cross Sectional

e22049 Background: The risk stratification of NSCLC on the basis of molecular information is a key approach in the clinical management of patients with the disease. MET is the receptor for HGF and is present in the membrane of NSCLC cells. The most common genetic alteration associated with MET is the gene amplification. Methods: Two independent investigators applied parallel search strategies with the terms "MET" AND "lung cancer", "MET" AND "NSCLC", "met gene copy number" AND "prognosis" in PubMed through November 2012. We selected the studies that investigated the association of MET gene copy number with prognosis. A quality score that assessed the lab methods, the generalizability and the analysis, was assigned to each study that was finally included in the analysis. Results: Among 791 studies that were identified in the initial search, we retrieved 8 cross sectional studies on retrospective cohorts with adequate data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Among the studies, 5 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. All 8 studies used tissue from surgically resected specimens. MET gene copy number predicted worse overall survival when all studies were combined in a fixed effects model (HR=1.35, 95% CI 1.17-1.57). We calculated the I2 statistic to assess heterogeneity (I2=44%, p=0.09). There were four studies where a higher gene copy number predicted a better outcome and four in which the opposite was true. The Egger’s regression intercept showed no significant publication bias (p=0.38). Conclusions: Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC.

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