Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Genomic and phenotypic heterogeneity of malignant tumors and their microenvironment
The advance of next-generation sequencing approaches facilitates the exploration of molecular characteristics across cancer genomes, transcriptomes, methylomes, and many other levels. The increasing number of sequenced tumor samples reveals the molecular heterogeneity between patients, primary and metastatic lesions and cells as well as molecular mechanisms associated with metastatic dissemination or treatment resistance. These potentially can influence tumor progression and therapeutic intervention. The first part of this thesis investigates the genomic landscape of Merkel cell carcinoma (MCC) cell lines. MCC is a rare and aggressive neuroendocrine skin cancer associated either with ultraviolet (UV)-light induced DNA damage or clonal integration of the Merkel cell polyomavirus (MCPyV). The associated genomic variations are well studied in tumor tissue, but not in MCC cell lines that are frequently used as preclinical models. Therefore, I analyzed whole-exome sequencing data of 3 UV- and 6 MCPyV-associated MCC cell lines demonstrating that their mutational landscape is congruent with MCC tumor tissue. UV-associated cell lines have a high tumor mutational burden (TMB), single-base substitution signatures (SBS) reflecting UV-light induced DNA damage, pathogenic variants in TP53 and RB1 genes and a high number of copy number variations (CNVs). In contrast, MCPyV-associated cell lines show only few mutations with no specific signature, but characteristic CNVs. We further found additional genomic heterogeneity with an amplified and overexpressed c-MYC in the UV-associated cell line UM-MCC34, indicating the presence of potential further MCC subtypes. The second part of this thesis analyzes the transcriptomic and cellular heterogeneity of oral cavity squamous cell carcinoma (OSCC). OSCC is caused by an abuse of tobacco- and alcohol consumption and frequently develops locoregional lymph node metastases. The metastatic spread is often mediated by epithelial-mesenchymal transition (EMT), in which cells change from a more ...
Genomic and phenotypic heterogeneity of malignant tumors and their microenvironment
The advance of next-generation sequencing approaches facilitates the exploration of molecular characteristics across cancer genomes, transcriptomes, methylomes, and many other levels. The increasing number of sequenced tumor samples reveals the molecular heterogeneity between patients, primary and metastatic lesions and cells as well as molecular mechanisms associated with metastatic dissemination or treatment resistance. These potentially can influence tumor progression and therapeutic intervention. The first part of this thesis investigates the genomic landscape of Merkel cell carcinoma (MCC) cell lines. MCC is a rare and aggressive neuroendocrine skin cancer associated either with ultraviolet (UV)-light induced DNA damage or clonal integration of the Merkel cell polyomavirus (MCPyV). The associated genomic variations are well studied in tumor tissue, but not in MCC cell lines that are frequently used as preclinical models. Therefore, I analyzed whole-exome sequencing data of 3 UV- and 6 MCPyV-associated MCC cell lines demonstrating that their mutational landscape is congruent with MCC tumor tissue. UV-associated cell lines have a high tumor mutational burden (TMB), single-base substitution signatures (SBS) reflecting UV-light induced DNA damage, pathogenic variants in TP53 and RB1 genes and a high number of copy number variations (CNVs). In contrast, MCPyV-associated cell lines show only few mutations with no specific signature, but characteristic CNVs. We further found additional genomic heterogeneity with an amplified and overexpressed c-MYC in the UV-associated cell line UM-MCC34, indicating the presence of potential further MCC subtypes. The second part of this thesis analyzes the transcriptomic and cellular heterogeneity of oral cavity squamous cell carcinoma (OSCC). OSCC is caused by an abuse of tobacco- and alcohol consumption and frequently develops locoregional lymph node metastases. The metastatic spread is often mediated by epithelial-mesenchymal transition (EMT), in which cells change from a more ...
Genomic and phenotypic heterogeneity of malignant tumors and their microenvironment
Horny, Kai (Autor:in) / Becker, Jürgen
02.02.2024
Hochschulschrift
Elektronische Ressource
Englisch
Cations in Malignant and Benign Brain Tumors
| Online Contents | 1996
| Wiley | 2024
| Wiley | 2024