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

Abstract 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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Correlating genomic copy number alterations with clinicopathologic findings in a case series of hepatocellular carcinoma

10.21203/rs.3.rs-40266/v2 ◽

2020 ◽

Author(s):

Gang Peng ◽

Hongyan Chai ◽

Weizhen Ji ◽

Yufei Lu ◽

Shengming Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number ◽

Case Series ◽

Oligonucleotide Array ◽

Good Survival ◽

Survival Outcomes ◽

Copy Number Alterations ◽

Acgh Analysis ◽

Clinicopathologic Findings ◽

Grade Iii

Abstract 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%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated 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 correlated 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 correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

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Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma

BMC Medical Genomics ◽

10.1186/s12920-021-00998-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Gang Peng ◽

Hongyan Chai ◽

Weizhen Ji ◽

Yufei Lu ◽

Shengming Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number ◽

Oligonucleotide Array ◽

Good Survival ◽

Survival Outcomes ◽

Comparative Genomic ◽

Copy Number Alterations ◽

Acgh Analysis ◽

Clinicopathologic Findings ◽

Grade Iii

Abstract 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 cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. Methods aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. 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%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated 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 correlated 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 correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

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Sex-dependent differences in DNA copy number alterations in hepatocellular carcinoma

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00005 ◽

2012 ◽

Vol 32 (1) ◽

pp. 5-9 ◽

Cited By ~ 1

Author(s):

Bing-ji WEN ◽

Wen-ming CONG ◽

Ai-zhong WANG ◽

Song-qin HE ◽

Hong-mei JIANG ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number ◽

Copy Number Alterations ◽

Dna Copy Number ◽

Dna Copy Number Alterations

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Convergent Evolution of Copy Number Alterations in Multi-Centric Hepatocellular Carcinoma

Scientific Reports ◽

10.1038/s41598-019-40843-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Carolin Lackner ◽

Luca Quagliata ◽

William Cross ◽

Sebastian Ribi ◽

Karl Heinimann ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number ◽

Convergent Evolution ◽

Copy Number Alterations

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Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q

International Journal of Cancer ◽

10.1002/ijc.23901 ◽

2008 ◽

Vol 123 (12) ◽

pp. 2808-2815 ◽

Cited By ~ 60

Author(s):

Tae-Min Kim ◽

Seon-Hee Yim ◽

Seung-Hun Shin ◽

Hai-Dong Xu ◽

Yu-Chae Jung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Implication ◽

Copy Number ◽

Copy Number Alterations

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COL1A1 copy number alterations detected in array-based comparative genomic hybridization (aCGH) inmyeloproliferative neoplasms: Implications for molecular pathogenesis and targeted therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22139 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22139-e22139

Author(s):

Michael R. Savona ◽

Pranil Chandra ◽

Zeqiang Ma ◽

Shile Liang ◽

R. Seth Cooper ◽

...

Keyword(s):

Comparative Genomic Hybridization ◽

Copy Number ◽

Myeloproliferative Neoplasms ◽

Normal Karyotype ◽

Dermatofibrosarcoma Protuberans ◽

Molecular Pathogenesis ◽

Oligonucleotide Array ◽

Comparative Genomic ◽

Copy Number Alterations ◽

Genomic Hybridization

e22139 Background: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of tumors marked by clonal proliferation of myeloid cells with variable marrow changes and clinical findings. Though progress has been made since the discovery of the JAK2V617F mutation, few data exist on the genetic distinction amongst these disorders, or pathogenesis of fibrosis seen in MPNs. Methods: Array-based comparative genomic hybridization (aCGH) was performed on genomic DNA extracted from marrow aspirate using an Agilent 180K oligonucleotide array platform in order to discover recurrent genetic aberrations, cooperating mutations, and gain insight into the hierarchy of molecular pathogenesis of fibrosis. BM aspirate from 17 pts were analyzed. Copy number alterations (CNAs) were compared to a reference set and mapped to functional genes. Genes with CNA were subjected to gene ontology, pathway and clustering analysis. Results: aCGH yielded copy number gains or losses in 17 out of 17 cases, 11 of which had normal karyotype and/or FISH. Numerous CNAs were identified within genes found in a variety of cellular pathways. In particular, alterations in COL1A1, NFKb and PDGFRb were implicated in this MPN cohort in 12, 8, and 6, pts, respectively. Interestingly, only patients with COL1A1 CNA had aberrancy within NFKb and PDGFRb. The remaining 5 pts had abnormal aCGH, but normal signals at these 3 genes. Conclusions: aCGH is a valuable tool which may be used to distinguish MPNs, particularly when standard testing does not. The presence of the COL1A1 aberration in 12/17 cases edifies evolving study of the role of TGFB superfamily in development of fibrosis and provides potential targets to exploit in the treatment of MPNs. Though aberrations within COL1A1 have not been previously reported in MPNs, a gene fusion involving COL1A1 and PDGFRb is found in 90% of dermatofibrosarcoma protuberans. The cooperation between these genes is currently under study in a larger cohort of pts with MPNs. [Table: see text]

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