Intra- and inter-tumoral heterogeneity of liver metastases in a patient with uveal melanoma
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PROVIDER: PRJNA734609 | ENA |
REPOSITORIES: ENA
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Project description:Tumour heterogeneity has been the main obstacle to the clinical efficacy of targeted and immunotherapy in cancer. An accurate understanding and recognition of tumour heterogeneity is critical in the clinical management of cancer patients. Here, we utilised single-cell RNA sequencing (scRNA-seq) to uncover the intra- and inter-tumoural heterogeneity of liver metastases from a patient with metastatic uveal melanoma.
2021-09-12 | GSE176029 | GEO
Project description:Trunk events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma
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Project description:The inter-patient variability of tumor proteomes has been investigated on a large scale but many tumors display also intra-tumoral heterogeneity (ITH) regarding morphological and genetic features. To what extent the local proteome of tumors intrinsically differs remains largely unknown. Here, we used hepatocellular carcinoma (HCC) as a model system, to quantify both inter- and intra-tumor heterogeneity across human patient specimens with spatial resolution. We first defined proteomic features that robustly distinguish neoplastic from the directly adjacent non-neoplastic tissue by integrating proteomic data from human patient samples and genetically defined mouse models with available gene expression data. We then demonstrated the existence of intra-tumoral variations in protein abundance that re-occur across different patient samples, and affect clinically relevant proteins, even in the absence of obvious morphological differences or genetic alterations. Our work demonstrates the suitability and the benefits of using mass spectrometry based proteomics to analyze diagnostic tumor specimens with spatial resolution
2018-01-24 | PXD007052 | Pride
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
Project description:Intra-individual tumoral heterogeneity of ovarian serous adenocarcinomas
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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:A high percentage of uveal melanoma patients develop metastatic tumors that predominately occur in the liver. To identify genes associated with metastasis in this pathology, we studied 63 molecular profiles derived from gene expression microarrays performed from enuceated primary tumors. Metastasis free survival analysis was performed to obtain clinical and genomic variables associated to metastasis occurrence. We also compared within the 57 tumors with at least 36 months follow-up, 28 uveal melanoma from patients who developed liver metastases (meta1 group) with 29 tumors arising from patients without metastases (or later metastases, i.e. after 36 months) (meta0 group). The transcriptome of 63 uveal melanoma from enucleation of untreated patients were analyzed using Affymetrix U133plus2 Arrays.
2010-12-14 | E-GEOD-22138 | biostudies-arrayexpress
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: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