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| Status |
Public on Jul 05, 2019 |
| Title |
Trunk events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma [early CNV] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Introduction: According to the clonal model of tumor evolution, trunk alterations arise at early stages and are ubiquitous. Through the characterization of early stages of hepatocarcinogenesis, we aimed to identify trunk alterations in HCC and study their intra- and inter-tumor distribution in more advanced lesions. Methods: 151 samples representing the multi-step process of hepatocarcinogenesis were analyzed by targeted-sequencing and SNP array. Genes altered in early lesions [31 dysplastic nodules (DNs) and 38 small HCCs (sHCC)] were defined as trunk. The distribution of candidate trunk genes was explored in: a) different regions of large tumors [43 regions of 21 tumors, (2-3 regions/tumor)]; and b) different nodules of the same patient [39 multinodular tumors from 17 patients]. Multinodular lesions were classified as intrahepatic metastases (IMs) or synchronous tumors based on chromosomal aberrations. Results: TERT promoter mutations (10.5%) and broad copy-number aberrations in chromosomes 1 and 8 (3-7%) were identified as trunk gatekeepers in DNs and were maintained in sHCCs. Trunk drivers identified in sHCCs included TP53 (23%) and CTNNB1 (11%) mutations, and focal amplifications or deletions in known drivers (6%). Overall, TERT, TP53 and CTNNB1 mutations were the most frequent trunk events in early stages. 89% of mutations in these genes were shared between different regions of large tumors. In multinodular HCCs, 35% of patients harbored IMs. 85% of mutations in TERT, TP53 and/or CTNNB1 were retained in primary and metastatic tumors. Conclusions: Trunk events in early stages (TERT, TP53, CTNNB1 mutations) were ubiquitous across different regions of the same tumor and between primary and metastatic nodules in >85% of cases. This concept supports the knowledge that single biopsies would suffice to capture trunk mutations in HCC.
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| Overall design |
Paraffin-embedded and fresh-frozen samples representing early steps of hepatocarcinogenesis were collected and gDNA was extracted. This cohort comprised: 29 dysplastic nodules (DN) -including low-grade and high-grade dysplasia (LGDN and HGDN)-; and 17 small tumors (sHCCs) -including 6 very-early and 11 early HCCs (veHCC and eHCC). When available matched cirrhotic tissues was also collected and extracted. Comparative Genomic Hybridization analysis was done using HumanOmniExpress-24 v1.1 BeadChip (Illumina) according to manufacturer’s protocols. Previous treatment with the Infinium FFPE restoration kit (Illumina) was performed for FFPE samples. Log R ratio (LRR, reflecting total copy number) and B-allele frequency (BAF) obtained from GenomeStudio were used for CNV detection.
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| Contributor(s) |
Llovet JM, Zhang Z, Hao K |
| Citation(s) |
28843658 |
| Submission date |
May 07, 2017 |
| Last update date |
Jul 06, 2019 |
| Contact name |
Sara Torrecilla |
| Organization name |
IDIBAPS
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| Lab |
Liver Cancer Translational Research Laboratory
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| Street address |
Rossello Street, 149
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| City |
Barcelona |
| State/province |
Catalonia |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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| Platforms (1) |
| GPL22678 |
HumanOmniExpress-24 v1.1 BeadChip [SNP_ID version] |
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| Samples (82)
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| This SubSeries is part of SuperSeries: |
| GSE98620 |
Trunk events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma |
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| Relations |
| BioProject |
PRJNA385737 |
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