{"id":{"repo_id":"bielefeld","oai_identifier":"oai:pub.uni-bielefeld.de:2987114"},"canonical_url":"https://search.dev.ndltd.org/etd/bielefeld/oai:pub.uni-bielefeld.de:2987114","repository":{"repo_id":"bielefeld","name":"Universität Bielefeld","base_url":"https://pub.uni-bielefeld.de/oai"},"display":{"title":"Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing","abstract":"Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing<br /> Carsten Hain<br /> #### Abstract Cutaneous T-cell lymphoma (CTCL) are a group of diseases with heterogenous genetic alterations. In general, there are recurrent copy-number variants and rare, single nucleotide variants that ultimately cluster in a limited number of pathways, including JAK-STAT- and T-cell receptor signaling. Currently, there is a lack of knowledge about the genetic changes in early and treatment-naïve patients, which makes a correlation between genetics and variable disease progression impossible.<br /> In this work, the copy-number landscape of the rare CTCL subtype, Sézary syndrome, was further detailed using whole-exome sequencing data, and the frequency of whole-genome duplications was determined. Furthermore, molecular timing of large copy-number variants was quantified. Specifically, the STAT5-bearing chr17q amplification arises very early in tumor evolution, which underlines the central function of this signaling pathway. Analysis of samples from the most common CTCL subtype, mycosis fungoides, revealed a low tumor cell fraction in bulk skin biopsies. To tackle this issue, an approach for enrichment of malignant cells was applied. This allowed a more confident calling of somatic variants, especially for copy-number variants. Analysis of mycosis fungoides samples with a high tumor cell fraction revealed a severely altered copy-number landscape. The use of Oxford Nanopore long-read sequencing enabled a precise elucidation of structural variants and uncovered multiple classes of complex structural variants underlying the recurrent losses of common tumor suppressor genes in mycosis fungoides.<br /> In summary, this work contributes to the current understanding of CTCL genetics, highlights the complexities that hinders further progress in uncovering the genetic basis of this disease, and first-time uses third-generation sequencing technologies to unravel the complex genetics of mycosis fungoides.","abstract_html":"Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing&lt;br /&gt; Carsten Hain&lt;br /&gt; #### Abstract Cutaneous T-cell lymphoma (CTCL) are a group of diseases with heterogenous genetic alterations. In general, there are recurrent copy-number variants and rare, single nucleotide variants that ultimately cluster in a limited number of pathways, including JAK-STAT- and T-cell receptor signaling. Currently, there is a lack of knowledge about the genetic changes in early and treatment-naïve patients, which makes a correlation between genetics and variable disease progression impossible.&lt;br /&gt; In this work, the copy-number landscape of the rare CTCL subtype, Sézary syndrome, was further detailed using whole-exome sequencing data, and the frequency of whole-genome duplications was determined. Furthermore, molecular timing of large copy-number variants was quantified. Specifically, the STAT5-bearing chr17q amplification arises very early in tumor evolution, which underlines the central function of this signaling pathway. Analysis of samples from the most common CTCL subtype, mycosis fungoides, revealed a low tumor cell fraction in bulk skin biopsies. To tackle this issue, an approach for enrichment of malignant cells was applied. This allowed a more confident calling of somatic variants, especially for copy-number variants. Analysis of mycosis fungoides samples with a high tumor cell fraction revealed a severely altered copy-number landscape. The use of Oxford Nanopore long-read sequencing enabled a precise elucidation of structural variants and uncovered multiple classes of complex structural variants underlying the recurrent losses of common tumor suppressor genes in mycosis fungoides.&lt;br /&gt; In summary, this work contributes to the current understanding of CTCL genetics, highlights the complexities that hinders further progress in uncovering the genetic basis of this disease, and first-time uses third-generation sequencing technologies to unravel the complex genetics of mycosis fungoides.","abstract_has_math":false,"creators":["Hain, Carsten"],"institution":"Universität Bielefeld","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-02-02","date_published":"2024-02-02","updated_at":"2026-07-27T18:50:07Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://pub.uni-bielefeld.de/record/2987114","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Hain, Carsten"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek Bielefeld"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Universität Bielefeld"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing<br /> Carsten Hain<br /> #### Abstract Cutaneous T-cell lymphoma (CTCL) are a group of diseases with heterogenous genetic alterations. In general, there are recurrent copy-number variants and rare, single nucleotide variants that ultimately cluster in a limited number of pathways, including JAK-STAT- and T-cell receptor signaling. Currently, there is a lack of knowledge about the genetic changes in early and treatment-naïve patients, which makes a correlation between genetics and variable disease progression impossible.<br /> In this work, the copy-number landscape of the rare CTCL subtype, Sézary syndrome, was further detailed using whole-exome sequencing data, and the frequency of whole-genome duplications was determined. Furthermore, molecular timing of large copy-number variants was quantified. Specifically, the STAT5-bearing chr17q amplification arises very early in tumor evolution, which underlines the central function of this signaling pathway. Analysis of samples from the most common CTCL subtype, mycosis fungoides, revealed a low tumor cell fraction in bulk skin biopsies. To tackle this issue, an approach for enrichment of malignant cells was applied. This allowed a more confident calling of somatic variants, especially for copy-number variants. Analysis of mycosis fungoides samples with a high tumor cell fraction revealed a severely altered copy-number landscape. The use of Oxford Nanopore long-read sequencing enabled a precise elucidation of structural variants and uncovered multiple classes of complex structural variants underlying the recurrent losses of common tumor suppressor genes in mycosis fungoides.<br /> In summary, this work contributes to the current understanding of CTCL genetics, highlights the complexities that hinders further progress in uncovering the genetic basis of this disease, and first-time uses third-generation sequencing technologies to unravel the complex genetics of mycosis fungoides."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing"]}]}],"canonical_facts":{"dc:creator":["Hain, Carsten"],"dc:description.abstract":["Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing<br /> Carsten Hain<br /> #### Abstract Cutaneous T-cell lymphoma (CTCL) are a group of diseases with heterogenous genetic alterations. In general, there are recurrent copy-number variants and rare, single nucleotide variants that ultimately cluster in a limited number of pathways, including JAK-STAT- and T-cell receptor signaling. Currently, there is a lack of knowledge about the genetic changes in early and treatment-naïve patients, which makes a correlation between genetics and variable disease progression impossible.<br /> In this work, the copy-number landscape of the rare CTCL subtype, Sézary syndrome, was further detailed using whole-exome sequencing data, and the frequency of whole-genome duplications was determined. Furthermore, molecular timing of large copy-number variants was quantified. Specifically, the STAT5-bearing chr17q amplification arises very early in tumor evolution, which underlines the central function of this signaling pathway. Analysis of samples from the most common CTCL subtype, mycosis fungoides, revealed a low tumor cell fraction in bulk skin biopsies. To tackle this issue, an approach for enrichment of malignant cells was applied. This allowed a more confident calling of somatic variants, especially for copy-number variants. Analysis of mycosis fungoides samples with a high tumor cell fraction revealed a severely altered copy-number landscape. The use of Oxford Nanopore long-read sequencing enabled a precise elucidation of structural variants and uncovered multiple classes of complex structural variants underlying the recurrent losses of common tumor suppressor genes in mycosis fungoides.<br /> In summary, this work contributes to the current understanding of CTCL genetics, highlights the complexities that hinders further progress in uncovering the genetic basis of this disease, and first-time uses third-generation sequencing technologies to unravel the complex genetics of mycosis fungoides."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek Bielefeld"],"dc:title":["Exploring the genetic landscape in cutaneous T-cell lymphoma with short- and long-read sequencing"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Universität Bielefeld"]},"updated_at":"2026-07-27T18:50:07Z"}