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Title:
Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma | BMC Cancer
Description:
Background Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies. Methods We analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR. Results Somatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r β₯ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r β₯ 0.8 (p = 0.01). All IM cases were highly similar; that is, r β₯ 0.8 (p = 0.025). Conclusions The overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.
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tumors, methylation, article, aberrations, multiple, hepatocellular, pubmed, google, scholar, cas, carcinoma, patients, common, cancer, hcc, analysis, chromosomal, genes, table, clinical, tumor, cases, somatic, mutations, patient, dna, genetic, data, human, carcinogenesis, molecular, genomic, file, figure, number, authors, patterns, similar, samples, additional, journal, multicentric, promoter, pcr, results, pattern, diagnosis, mutation, values, research,
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open access article array-comparative genomic hybridization organ-confined prostate adenocarcinoma single-nucleotide polymorphism arrays single-nucleotide polymorphism scanning multiple tumour nodules pre-publication history article download pdf comparative genomic hybridization human hepatocellular carcinoma uk/genetics/cgp/cosmic/ multicentric hepatocellular carcinoma high-resolution melting analysis recurrent hepatocellular carcinoma quantitative methylation-specific pcr full size image multiple hepatocellular carcinoma small hepatocellular carcinoma tumor-suppressor p53 gene privacy choices/manage cookies recurrent hepatocellular carcinomas functional liver reserve neoplastic liver cells primary liver cancer multiple hepatocellular carcinomas article taniguchi comparative lesion sequencing related subjects kikuya kato full access human molecular genetics recurrent metastatic nodules biomed central bmc cancer 10 high-resolution melting high-resolution melting [24] full size table cancer-related genes multiple genomic aberrations gene set included entire genomic sequencing cancer-specific methylation authorsβ original file promoter methylation analysis european economic area salt lake city solid scientific basis polymerase chain reaction infrequent chromosomal aberrations chromosomal aberrations suggests
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headline:Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma
description:Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies. We analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR. Somatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r β₯ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r β₯ 0.8 (p = 0.01). All IM cases were highly similar; that is, r β₯ 0.8 (p = 0.025). The overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.
datePublished:2010-10-06T00:00:00Z
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Somatic Mutation
Promoter Methylation
Chromosomal Aberration
Multiple Tumor
Multicentric Carcinogenesis
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
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headline:Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma
description:Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies. We analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR. Somatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r β₯ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r β₯ 0.8 (p = 0.01). All IM cases were highly similar; that is, r β₯ 0.8 (p = 0.025). The overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.
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Somatic Mutation
Promoter Methylation
Chromosomal Aberration
Multiple Tumor
Multicentric Carcinogenesis
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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