Trunk events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma
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PROVIDER: PRJNA385729 | ENA |
REPOSITORIES: ENA
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Project description: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.
2019-07-05 | GSE102451 | GEO
Project description: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.
2019-07-05 | GSE102383 | GEO
Project description: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.
2019-07-05 | GSE98617 | GEO
Project description: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.
2019-07-05 | GSE98619 | GEO
Project description: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.
2019-07-05 | GSE98618 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-07-05 | GSE98620 | GEO
Project description:Hereditary endocrine neoplasias, including phaeochromocytoma/paraganglioma (PPGL) and medullary thyroid cancer (MTC), are caused by autosomal dominant mutations in a multitude of familial cancer genes. A common feature of these diseases is the presentation of multiple primary tumours or multifocal disease representing independent tumour clones that have arisen from the same initiating genetic lesion but have undergone independent clonal evolution. Such tumours provide a unique opportunity to discover common co-operative changes required for tumorigenesis while controlling for the genetic background of the individual. We performed an in-depth genomic analysis of synchronous and metachronous tumours from five patients harbouring germline mutations in the genes SDHB, RET and MAX. Using whole exome sequencing and high-density SNP-arrays we analyzed between two and four primary tumours from each patient. Furthermore, we applied multi-regional sampling to assess intra-tumoral heterogeneity and clonal evolution in two cases involving PPGL and MTC, respectively. Heterogeneous patterns of genomic change existed between synchronous or metachronous tumours with evidence of branching evolution. We observed striking examples of evolutionary convergence involving the same rare somatic copy-number events in synchronous primary PPGL. Convergent events also occurred during clonal evolution of metastatic MTC. These observations suggest that genetic or epigenetic changes acquired early within precursor cells, or pre-existing within the genetic background of the individual, create contingencies that determine the evolutionary trajectory of the tumour.
2017-02-02 | GSE94378 | GEO
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Project description:Neural crest cells migrate extensively in vertebrate embryos to populate diverse derivatives including ganglia of the peripheral nervous system. Little is known about the molecular mechanisms that tell migrating trunk neural crest cells to settle at selected sites in the embryo by ceasing migration and initiating differentiation programs.
2019-11-02 | GSE139859 | GEO