Survival analysis of the most frequent Single Nucleotide Variants in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
J Daza ◽  
T Itzel ◽  
MP Ebert ◽  
A Teufel
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Single Nucleotide Variants ◽  
Single Nucleotide

scholarly journals Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers

2021 ◽  
Author(s):  
Zachary L Skidmore ◽  
Jason Kunisaki ◽  
Yiing Lin ◽  
Kelsy C Cotto ◽  
Erica K Barnell ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Copy Number Variants ◽  
Genomic Analysis ◽  
Structural Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Tert Promoter Mutations ◽  
Somatic Alterations ◽  
Differential Gene ◽  
Promoter Mutations

Background: Liver cancer is the second leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) risk factors include chronic hepatitis, cirrhosis, and alcohol abuse, whereby tumorigenesis is induced through inflammation and subsequent fibrotic response. However, a subset of HCC arises in non-cirrhotic livers. We characterized the genomic and transcriptomic landscape of non-cirrhotic HCC to identify features underlying the disease's development and progression. Methods: Whole genome and transcriptome sequencing was performed on 30 surgically resectable tumors comprised of primarily of non-cirrhotic HCC and adjacent normal tissue. Using somatic variants, capture reagents were created and employed on an additional 87 cases of mixed cirrhotic/non-cirrhotic HCC. Cases were analyzed to identify viral integrations, single nucleotide variants (SNVs), insertions and deletions (INDELS), copy number variants, loss of heterozygosity, gene fusions, structural variants, and differential gene expression. Results: We detected 3,750 SNVs/INDELS and extensive CNVs and expression changes. Recurrent TERT promoter mutations occurred in >52% of non-cirrhotic discovery samples. Frequently mutated genes included TP53, CTNNB1, and APOB. Cytochrome P450 mediated metabolism was significantly downregulated. Structural variants were observed at MACROD2, WDPCP, and NCKAP5 in >20% of samples. Furthermore, NR1H4 fusions involving gene partners EWSR1, GNPTAB, and FNIP1 were detected and validated in 2 non-cirrhotic samples. Conclusion: Genomic analysis can elucidate mechanisms that may contribute to non-cirrhotic HCC tumorigenesis. The comparable mutational landscape between cirrhotic and non-cirrhotic HCC supports previous work suggesting a convergence at the genomic level during disease progression. It is therefore possible genomic-based treatments can be applied to both HCC subtypes with progressed disease.

scholarly journals MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Soon Sun Kim ◽  
Jung Woo Eun ◽  
Ji-Hye Choi ◽  
Hyun Goo Woo ◽  
Hyo Jung Cho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Circulating Tumor Dna ◽  
Single Nucleotide Variants ◽  
Poor Overall Survival ◽  
Single Nucleotide ◽  
Strong Basis ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction ◽  
Tumor Dna

Abstract Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.

Five-year Survival Analysis of a Cohort of Hepatocellular Carcinoma Patients Who Treated at the National Cancer Center, Korea

2007 ◽  
Vol 13 (4) ◽  
pp. 530 ◽  
Author(s):  
Kyung Woo Park ◽  
Joong-Won Park ◽  
Tae Hyun Kim ◽  
Jun Il Choi ◽  
Seong Hoon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Cancer Center

miR-224 is an early-stage biomarker of hepatocellular carcinoma with miR-224 and miR-125b as prognostic biomarkers

2020 ◽  
Vol 14 (15) ◽  
pp. 1485-1500
Author(s):  
Lichao Yang ◽  
Chunmeng Wei ◽  
Yasi Li ◽  
Xiao He ◽  
Min He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Survival Analysis ◽  
Sensitivity And Specificity ◽  
Poor Prognosis ◽  
Early Stage ◽  
Meta Analysis ◽  
Benign Lesion ◽  
Diagnostic Efficiency ◽  
Low Expression

Aim: The aim was to systematically investigate the miRNA biomarkers for early diagnosis of hepatocellular carcinoma (HCC). Materials & methods: A systematic review and meta-analysis of miRNA expression in HCC were performed. Results: A total of 4903 cases from 30 original studies were comprehensively analyzed. The sensitivity and specificity of miR-224 in discriminating early-stage HCC patients from benign lesion patients were 0.868 and 0.792, which were superior to α-fetoprotein. Combined miR-224 with α-fetoprotein, the sensitivity and specificity were increased to 0.882 and 0.808. Prognostic survival analysis showed low expression of miR-125b and high expression of miR-224 were associated with poor prognosis. Conclusion: miR-224 had a prominent diagnostic efficiency in early-stage HCC, with miR-224 and miR-125b being valuable in the prognostic diagnosis.

scholarly journals Survival analysis of sorafenib in hepatocellular carcinoma patients with microvascular invasion after hepatectomy

2018 ◽  
Vol 29 ◽  
pp. viii679
Author(s):  
Z. Zhang ◽  
Y. Huang ◽  
Y. Zhou ◽  
J. Yang ◽  
K. Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Microvascular Invasion

Single-Nucleotide Variants in microRNAs Sequences or in their Target Genes Might Influence the Risk of Epilepsy: A Review

2021 ◽  
Author(s):  
Renata Parissi Buainain ◽  
Matheus Negri Boschiero ◽  
Bruno Camporeze ◽  
Paulo Henrique Pires de Aguiar ◽  
Fernando Augusto Lima Marson ◽  
...  
Keyword(s):  
Target Genes ◽  
Single Nucleotide Variants ◽  
Single Nucleotide

scholarly journals Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Nayoung Han ◽  
Jung Mi Oh ◽  
In-Wha Kim
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Gain ◽  
Copy Number Variations ◽  
Gene Gain ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Control And Prevention

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

scholarly journals Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Hélène Morel ◽  
Olivier Milleron ◽  
Laurent Gouya ◽  
Christine Francannet ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Somatic Mosaicism ◽  
Variant Calling ◽  
Copy Number Variations ◽  
Pathogenic Variant ◽  
Single Nucleotide Variants ◽  
Bioinformatics Analyses ◽  
Single Nucleotide ◽  
Fbn1 Gene ◽  
Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

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