Dissolving heterogeneity in cancer:
Gespeichert in:
| Beteilige Person: | |
|---|---|
| Format: | Hochschulschrift/Dissertation Buch |
| Sprache: | Englisch |
| Veröffentlicht: |
2013
|
| Schlagwörter: | |
| Links: | http://epub.uni-regensburg.de/28058/ https://nbn-resolving.org/urn:nbn:de:bvb:355-epub-280586 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025936876&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| Umfang: | III, 151 S. Ill., graph. Darst. |
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Datensatz im Suchindex
| DE-BY-TUM_katkey | 1925671 |
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| adam_text | IMAGE 1
CONTENTS
SUMMARY 1
INTRODUCTION A N D OUTLINE 3
1 METHODS 7
1.1 SUMMARIZING GENE EXPRESSION PROFILES: INDEXING 7
1.2 EXPLORATIVE METHODS 12
1.2.1 HIERARCHICAL CLUSTERING 12
1.2.2 CONSENSUS CLUSTERING 13
1.2.3 GUIDED CLUSTERING 15
1.3 THE BIOCONDUCTOR PACKAGE LIMMA 17
1.4 GENE ENRICHMENT 18
1.4.1 OVERREPRESENTATION ANALYSIS 18
1.4.2 GENE SET ENRICHMENT ANALYSIS 19
1.4.3 THE BIOCONDUCTOR PACKAGE ORDERED LIST 21
1.5 CLASSIFICATION: PREDICTION ANALYSIS OF MICROARRAYS 22
1.6 SURVIVAL ANALYSIS 24
1.6.1 SURVIVAL AND HAZARD 24
1.6.2 KAPLAN-MEIER SURVIVAL ESTIMATE 25
1.6.3 THE LOG-RANK TEST 26
1.6.4 COX PROPORTIONAL HAZARDS MODEL 26
2 BRAIN TUMOURS 29
2.1 BIOLOGICAL INTRODUCTION 29
2.2 T H E ORDER O F GENETIC PERTURBATIONS DIRECTS T H E DEVELOPMENT OF
BRAIN TUMOUR TYPES 32
2.2.1 MOTIVATION 32
2.2.2 OVER-EXPRESSION OF MULTIPLE GENES LEADS TO ONCOGENIC TRANSFORMA
TION OF P 5 3 - / - POSTNATAL NSC/NPCS 32
2.2.3 MICROARRAY HYBRIDIZATION AND PREPROCESSING 33
HTTP://D-NB.INFO/1037276868
IMAGE 2
CONTENTS
2.2.4 OVER-EXPRESSION OF HRAS OR MYC ALONE OR IN COMBINATION LEADS TO
THE DEVELOPMENT OF THREE BRAIN TUMOUR TYPES 33
2.2.5 CLUSTERING HIGHLIGHTS THE THREE HISTOLOGICALLY DIFFERENT TUMOUR
TYPES 34
2.2.6 IDENTIFICATION OF DIFFERENT GENE EXPRESSION PATTERNS FOR THE THREE
TUMOUR TYPES 34
2.2.7 HISTOLOGICAL AT/RT-LIKE TUMOUR ARE RELATED TO ER-STRESS 38
2.2.8 DEFINING A MOLECULAR SIGNATURE DIFFERENTIATING BETWEEN THREE TU
MOUR TYPES 39
2.2.9 THE CNS PNET PHENOTYPE INDUCED BY M Y C IS UNSTABLE AND
CAN BE CONVERTED INTO THE AT/RT-LIKE TUMOUR TYPE 40
2.2.10 DISCUSSION 43
2.3 GENE EXPRESSION DATA O F DIFFERENT GLIOBLASTOMA-DERIVED CSC IN
DICATE DIFFERENT CELLS O F ORIGIN 46
2.3.1 MOTIVATION 46
2.3.2 MICROARRAY PREPROCESSING AND QUALITY CONTROL 47
2.3.3 IDENTIFICATION OF TWO DIFFERENT GROUPS OF GBM CSC LINES 47
2.3.4 ASSOCIATING UNIQUELY EXPRESSED GENES WITH THE TWO DIFFERENT GROUPS
OF GBM CSC LINES 49
2.3.5 THE DIFFERENCE BETWEEN THE TWO TYPES OF GBM CSC LINES IS INDE
PENDENT OF GROWTH PATTERN 53
2.3.6 DEFINING A 24-GENE-SIGNATURE DIFFERENTIATING BETWEEN THE TWO TYPES
OF GBM CSCS 55
2.3.7 PREDICTION OF CSC AND FETAL NEURAL STEM CELL LINES USING THE
24-GENE-SIGNATURE 57
2.3.8 COMPARISON OF OUR CLASSIFICATION SYSTEM WITH THE SUBGROUPS RE
LATED TO THE 35-GENE-SIGNATURE 59
2.3.9 DISCUSSION 60
2.4 GLIOBLASTOMA CSC SUBTYPE DETERMINES T H E DEGREE O F IMMUNE
INFILTRATION 62
2.4.1 MOTIVATION 62
2.4.2 MICROAXRAY HYBRIDIZATION AND PREPROCESSING 63
2.4.3 PRONEURAL GBM SHOW A REDUCED IMMUNE INFILTRATION 63
2.4.4 TGF/3 RESPONSIVENESS IS DETERMINED BY THE EXPRESSION OF TGFR2 63
2.4.5 MESENCHYMAL-LIKE CSC LINES ARE RESPONSIVE TO TGF/3 TREATMENT . 64
2.4.6 DEFINING TGF/3 TARGET GENES AND A TGF/3 RESPONSE INDEX . . . . 65
2.4.7 ASSOCIATING TGF/3 RESPONSE WITH THE TYPE OF GBM CSC LINE . . 66
2.4.8 TGF/3 MEDIATES IMMUNOSUPPRESSION IN PRONEURAL-LIKE CSC . . . 68
II
IMAGE 3
CONTENTS
2.4.9 DISCUSSION 70
3 LYMPHOMA 7 3
3.1 BIOLOGICAL INTRODUCTION 73
3.1.1 BURKITT S LYMPHOMA (BL) 74
3.1.2 DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) 75
3.2 PATHWAY ACTIVITIES IN HUMAN TRANSFORMED G C B CELLS AND LYM P H O M
A 77
3.2.1 MOTIVATION 77
3.2.2 STROMAL SIGNALS AFFECTING B CELLS 78
3.2.3 THE EFFECT OF STROMAL SIGNALS ON BL2 CELLS 80
3.2.4 GENE EXPRESSION PATTERNS INDUCED B Y STROMAL EFFECTS IN BL2
INDICATE HIGH PATHWAY ACTIVATION IN DLBCL 80
IDENTIFYING GLOBAL GENE EXPRESSION CHANGES 80
LISTS OF AFFECTED GENES OVERLAP SIGNIFICANTLY ACROSS STROMAL STIMULI 83
3.2.5 IDENTIFICATION O F ACTIVATION INDICES IN DLBCL PATIENTS
T H A T ARE UNIQUE FOR A SPECIFIC STROMAL STIMULUS 87
INDICES HOLD INDEPENDENT PROGNOSTIC INFORMATION IN DLBCLS . . 91
GCB-LIKE LYMPHOMAS AXE CHARACTERIZED BY UNBALANCED BCR AND CD40
SIGNALING 93
HIGH C-MYC ACTIVITY IS ASSOCIATED WITH A LOW BCR.L INDEX . . . . 94
DISCUSSION 96
3.3 LEF1 EXPRESSION IS CHARACTERISTIC FOR SPORADIC B L 97
3.3.1 DATA 98
3.3.2 LEF1 IS ABERRANTLY EXPRESSED IN BL CELLS 99
3.3.3 IDENTIFYING LEF1 TARGET GENES IN BL CELLS 100
3.3.4 LEF1 KNOCKDOWN AFFECTS BL CELL PROLIFERATION 103
3.3.5 LEF1 TARGET GENES ARE AFFECTED BY /3-CATENIN AND W N T SIGNALING .
104 3.3.6 LEF1 ACTIVITY IS HIGHER IN MBLS COMPARED TO DLBCLS 106
3.3.7 DISCUSSION 108
APPENDIX 109
BIBLIOGRAPHY 127
LIST O F FIGURES 1 4 3
ABBREVIATIONS 145
CURRICULUM VITAE AND LIST O F PUBLICATIONS 146
III
|
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| language | English |
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| physical | III, 151 S. Ill., graph. Darst. |
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| publishDate | 2013 |
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| spellingShingle | Meyer, Katharina 1983- Dissolving heterogeneity in cancer Heterogenität (DE-588)4201275-2 gnd Krebs Medizin (DE-588)4073781-0 gnd Index (DE-588)4161483-5 gnd Genexpression (DE-588)4020136-3 gnd |
| subject_GND | (DE-588)4201275-2 (DE-588)4073781-0 (DE-588)4161483-5 (DE-588)4020136-3 (DE-588)4113937-9 |
| title | Dissolving heterogeneity in cancer |
| title_auth | Dissolving heterogeneity in cancer |
| title_exact_search | Dissolving heterogeneity in cancer |
| title_full | Dissolving heterogeneity in cancer vorgelegt von Katharina Meyer |
| title_fullStr | Dissolving heterogeneity in cancer vorgelegt von Katharina Meyer |
| title_full_unstemmed | Dissolving heterogeneity in cancer vorgelegt von Katharina Meyer |
| title_short | Dissolving heterogeneity in cancer |
| title_sort | dissolving heterogeneity in cancer |
| topic | Heterogenität (DE-588)4201275-2 gnd Krebs Medizin (DE-588)4073781-0 gnd Index (DE-588)4161483-5 gnd Genexpression (DE-588)4020136-3 gnd |
| topic_facet | Heterogenität Krebs Medizin Index Genexpression Hochschulschrift |
| url | http://epub.uni-regensburg.de/28058/ https://nbn-resolving.org/urn:nbn:de:bvb:355-epub-280586 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025936876&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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