Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

Wang, Dong; Zhu, Ziyu; Jiang, Hongmei; Zhu, Jiayi; Cong, Wen-ming; Wen, Bing; He, Song; Liu, Shu Fang

doi:10.1007/s12072-015-9642-0

Cited by 34 publications

(39 citation statements)

References 44 publications

(57 reference statements)

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“…E-S grading is determined by tumor histologic and cytologic ndings [27,28]. The general genomic pro le of CNAs from this case series showed a consistent pattern or shared similar CNAs from previous studies [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The most commonly seen CNAs in more than 30% of our case series, including gains of 1q, 5p and 8q and losses of 4q, 8p, 13q, 16q and 17p as shown in Fig.…”

Section: Discussionsupporting

confidence: 77%

“…A study focused on gene expression from gains of 20q identify candidate genes contributing to unfavorable outcomes for HCC. Overexpression of the DDX27, B4GALT5, RNF114, ZFP64 and PFDN4 associated signi cantly with vascular invasion, and high RNF114 expression also associated with advanced tumor stage [12]. We didn't nd signi cant association between CNAs and BCLC stage or recurrence status.…”

Section: Discussioncontrasting

confidence: 62%

“…In the past decade, integrated genomic analyses using aCGH, gene expression array, whole exome and genome sequencing had been applied to identify key genes and core pathways for the initiation and progression of HCC [7][8][9][10][11]. Recurrent CNAs correlating with stages and prognosis of HCC [12][13][14][15][16] and associating with infections by Hepatitis B or C virus [17][18] have been reported. Accumulated genetic and genomic data could be translated to clinical service for better genetic diagnosis and prognosis prediction.…”

Section: Introductionmentioning

confidence: 99%

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Correlating Genomic Copy Number Alterations with Clinicopathologic Findings in A Case Series of Hepatocellular Carcinoma

Peng

Chai

et al. 2020

Preprint

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Background: Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for a case series of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings.Methods: Survival outcomes from this case series were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means. Results: The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Correlation and clustering analyses noted that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely associated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly associated with worst prognosis. Conclusions: These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the association of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

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Section: Discussionsupporting

confidence: 77%

Section: Discussioncontrasting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Correlating Genomic Copy Number Alterations with Clinicopathologic Findings in A Case Series of Hepatocellular Carcinoma

Peng

Chai

et al. 2020

Preprint

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“…11p.15.4-5, Beckwith-Wiedemann cancer predisposition syndrome, T lymphoid leukemia (70–72); chr. 20q13.13, hepatocellular carcinoma (73)). We note as well that at the nucleotide level most of the NGS reads with recombination junctions contain structure-prone sequences predicted to be unstable under replication stress (G 300 , 2p22.3; G4, 2q12.2, 2q34, 7p15.3, 8q24.21, 11p15.4, 20q13.13; T 20 , 6q24.1; CTG 20 , 19p13.32).…”

Section: Discussionmentioning

confidence: 99%

FANCJ is essential to maintain microsatellite structure genome-wide during replication stress

Barthelemy

Leffak

2016

Nucleic Acids Res

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Microsatellite DNAs that form non-B structures are implicated in replication fork stalling, DNA double strand breaks (DSBs) and human disease. Fanconi anemia (FA) is an inherited disorder in which mutations in at least nineteen genes are responsible for the phenotypes of genome instability and cancer predisposition. FA pathway proteins are active in the resolution of non-B DNA structures including interstrand crosslinks, G quadruplexes and DNA triplexes. In FANCJ helicase depleted cells, we show that hydroxyurea or aphidicolin treatment leads to loss of microsatellite polymerase chain reaction signals and to chromosome recombination at an ectopic hairpin forming CTG/CAG repeat in the HeLa genome. Moreover, diverse endogenous microsatellite signals were also lost upon replication stress after FANCJ depletion, and in FANCJ null patient cells. The phenotype of microsatellite signal instability is specific for FANCJ apart from the intact FA pathway, and is consistent with DSBs at microsatellites genome-wide in FANCJ depleted cells following replication stress.

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“…Our results highlighted the top 4 frequent gain arms (20p, 8q, 1q, 20q) and the top 4 frequent loss arms (17p, 4q, 19p, 16q) in cfDNA of HCC patients. Several regions, such as gain of 1q, 8q24, 20q13.12-13.33 and loss of 17p, have been reported to be related with the prognosis of HCC patients (31,(33)(34)(35). In the present study, we focused on CNVs at chromosomal arm level.…”

Section: Discussionmentioning

confidence: 97%

Multiple-level copy number variations in circulating cell-free DNA for prognostic prediction of hepatocellular carcinoma with radical treatments

Wang¹,

Wang²,

Zhou³

et al. 2020

Preprint

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Background Copy number variations (CNVs) in circulating free DNA (cfDNA) are emerging as minimally invasive prognostic biomarkers for various cancers. However, little has been reported on the multiple-level analysis of cfDNA CNVs for hepatocellular carcinoma (HCC) patients with radical treatments. Methods Here, CNVs at genome-wide, chromosomal-arm and bin levels were analyzed in cfDNA from 117 HCC patients receiving radical treatments via low-coverage whole genome sequencing. Then, the relationship between cfDNA CNVs and clinical outcomes was explored. Our results showed that a concordant profile of CNVs was observed between cfDNA and tumor tissue DNA. Three genome-wide CNV indicators including tumor fraction (TFx), prediction score (P-score) and stability score (S-score) were calculated based on genome-wide cfDNA CNVs. Results Kaplan-Meier analysis showed that the patients with high TFx, P-score and S-score exhibited a significantly poorer overall survival (OS) and recurrence free survival (RFS) than those with low TFx, P-score and S-score, respectively (All P < 0.05). Furthermore, a group of high frequency cfDNA CNVs at chromosomal-arm level including loss of 4q, 17p, 19p and the gain of 8q, 1q clearly predicted prognosis of HCC patients. Finally, a bin-level risk score was constructed based on three most relevant prognostic bin regions identified by a LASSO model. Patients with high bin-score had a significantly poorer OS than those with low bin-score (P < 0.001). Conclusion Altogether, our study indicates that the multiple-level cfDNA CNVs are significantly associated with OS and RFS in HCC patients with radical treatments, suggesting that cfDNA CNVs detected by low-coverage WGS may be used as potential prognostic biomarkers of HCC patients.

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Multiple genes identified as targets for 20q13.12–13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma

Abstract: Gain at 20q13.12-13.33 is a prognostic marker of metastasis and death, and DDX27, B4GALT5, RNF114, ZFP64, and PFDN4 are probable target genes which may be involved together in the unfavorable outcomes of HCC patients.

Cited by 34 publications

References 44 publications

Correlating Genomic Copy Number Alterations with Clinicopathologic Findings in A Case Series of Hepatocellular Carcinoma

Correlating Genomic Copy Number Alterations with Clinicopathologic Findings in A Case Series of Hepatocellular Carcinoma

FANCJ is essential to maintain microsatellite structure genome-wide during replication stress

Multiple-level copy number variations in circulating cell-free DNA for prognostic prediction of hepatocellular carcinoma with radical treatments

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