Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma:
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| Sprache: | English |
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2023
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| 245 | 1 | 0 | |a Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |c vorgelegt von Feldmeyer, Leon Gabriel |
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Datensatz im Suchindex
| _version_ | 1804186449897062400 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
1
INTRODUCTION
........................................................................................................................................
1
1.1
BURKITT
LYMPHOMA
...................................................................................................................
1
1.1.1
CLINICAL
PRESENTATION
..........................................................................................................
2
1.1.2
DIAGNOSTIC
EVALUATION
..........................................................................................................
2
1.1.3
STAGING
AND
RISK
GROUP
STRATIFICATION
..................................................................................
2
1.1.4
THERAPY
AT
INITIAL
DIAGNOSIS
.................................................................................................
4
1.1.5
THERAPY
OF
RELAPSED
DISEASE................................................................................................
5
1.2
RECURRENTLY
MUTATED
GENES
IN
BL
...........................................................................................
6
1.2.1
TUMOUR
SUPPRESSOR
TP53
.....................................................................................................
6
1.3
STUDY
OBJECTIVES
......................................................................................................................
9
2
MATERIAL
AND
METHODS
......................................................................................................................
11
2.1
MATERIAL
................................................................................................................................
11
2.1.1
TECHNICAL
DEVICES
...............................................................................................................
11
2.1.2
CONSUMABLES
.....................................................................................................................
12
2.1.3
KITS
.....................................................................................................................................
12
2.1.4
BUFFERS,
MEDIA
AND
SOLUTIONS
.............................................................................................
12
2.1.5
OLIGONUCLEOTIDES
................................................................................................................
14
2.1.6
PLASMIDS
.............................................................................................................................
14
2.1.7
CELL
LINES
.............................................................................................................................
15
2.1.8
BACTERIA
STRAINS
..................................................................................................................
15
2.1.9
ANTIBODIES
..........................................................................................................................
15
2.1.10
SOFTWARE
......................................................................................................................
16
2.2
METHODS
................................................................................................................................
17
2.2.1
CELL
CULTURE
WORK
................................................................................................................
17
2.2.2
GENERAL
MOLECULAR
BIOLOGICAL
METHODS
..............................................................................
18
2.2.3
BACTERIA
..............................................................................................................................
21
2.2.4
CELL
LYSIS,
SDS-PAGE,
WESTERN
BLOT
...................................................................................
21
2.2.5
RT-QPCR
.............................................................................................................................
23
2.2.6
FUNCTIONAL
ASSAYS
...............................................................................................................
23
2.2.7
RNA
SEQUENCING
.................................................................................................................
23
2.2.8
STATISTICS
.............................................................................................................................
24
3
RESULTS...........................................................................................................................................
25
3.1
TP53
MUTATIONAL
STATUS
HAS
PROGNOSTIC
RELEVANCE
FOR
THE
RISK
OF
RELAPSE
.............................
25
3.2
GENOMIC
LOCALISATION
AND
ANALYSIS
OF
TP53
MUTATIONS
IN
PEDIATRIC
BURKITT
PATIENTS
............
26
3.3
ESTABLISHMENT
OF
TP53
OVEREXPRESSION
OF
POINT
MUTANTS
R175H,
R273H
AND
R273C
IN
BL-70
CELLS
27
3.3.1
VALIDATION
OF
TP53
OVEREXPRESSION
UPON
INDUCTION
WITH
DOXYCYCLINE..............................
29
3.3.2
OVEREXPRESSION
OF
TP53
POINT
MUTANTS
SHOW
INCREASE
IN
CELL
VIABILITY
.............................
29
3.4
ESTABLISHMENT
OF
A
TP53
KNOCKDOWN
IN
BL-70,
NAMALWA
AND
HELA
CELLS
...........................
30
3.4.1
VALIDATION
OF
TP53
KNOCKDOWN
UPON
INDUCTION
WITH
DOXYCYCLINE..................................
33
3.4.2
TP53
KNOCKDOWN
CELLS
SHOW
A
DECREASE
IN
CELL
VIABILITY
...................................................
34
3.5
GENE
EXPRESSION
PROFILING
OF
TP53
KNOCKDOWN
CELLS
.............................................................
35
3.5.1
GENERAL
INFORMATION
.........................................................................................................
35
3.5.2
GENES
UPREGULATED
TP53
KNOCKDOWN
CELLS
.......................................................................
35
3.5.3
GENES
DOWNREGULATED
IN
TP53
KNOCKDOWN
CELLS
..............................................................
37
3.5.4
CLUSTER
OF
DIFFERENTIATION
MARKERS
REGULATED
IN
TP53
KNOCKDOWN
ANALYSIS
......................
37
4
DISCUSSION
.......................................................................................................................................
39
4.1
TP53
GOF
MUTANTS
SHOW
INCREASE
IN
CELL
VIABILITY
IN
VITRO
....................................................
39
4.2
TP53
GOF
MUTANTS
AS
POTENTIAL
GENETIC
RISK
FACTOR
IN
PEDIATRIC
BL
.......................................
40
4.3
H1
LINKER
HISTONE
ISOFORMS
HL-5
AND
H1-0
ARE
DIFFERENTIALLY
REGULATED
IN
TP53
GOF
CELLS
..41
4.4
CD79A
DIFFERENTIALLY
REGULATED
IN
TP53
GOF
CELLS
.................................................................
42
5
CONCLUSION
......................................................................................................................................
44
6
REFERENCES
......................................................................................................................................
45
7
ACKNOWLEDGEMENTS
........................................................................................................................
57
8
CURRICULUM
VITAE
.............................................................................................................................
58
|
| adam_txt |
TABLE
OF
CONTENTS
1
INTRODUCTION
.
1
1.1
BURKITT
LYMPHOMA
.
1
1.1.1
CLINICAL
PRESENTATION
.
2
1.1.2
DIAGNOSTIC
EVALUATION
.
2
1.1.3
STAGING
AND
RISK
GROUP
STRATIFICATION
.
2
1.1.4
THERAPY
AT
INITIAL
DIAGNOSIS
.
4
1.1.5
THERAPY
OF
RELAPSED
DISEASE.
5
1.2
RECURRENTLY
MUTATED
GENES
IN
BL
.
6
1.2.1
TUMOUR
SUPPRESSOR
TP53
.
6
1.3
STUDY
OBJECTIVES
.
9
2
MATERIAL
AND
METHODS
.
11
2.1
MATERIAL
.
11
2.1.1
TECHNICAL
DEVICES
.
11
2.1.2
CONSUMABLES
.
12
2.1.3
KITS
.
12
2.1.4
BUFFERS,
MEDIA
AND
SOLUTIONS
.
12
2.1.5
OLIGONUCLEOTIDES
.
14
2.1.6
PLASMIDS
.
14
2.1.7
CELL
LINES
.
15
2.1.8
BACTERIA
STRAINS
.
15
2.1.9
ANTIBODIES
.
15
2.1.10
SOFTWARE
.
16
2.2
METHODS
.
17
2.2.1
CELL
CULTURE
WORK
.
17
2.2.2
GENERAL
MOLECULAR
BIOLOGICAL
METHODS
.
18
2.2.3
BACTERIA
.
21
2.2.4
CELL
LYSIS,
SDS-PAGE,
WESTERN
BLOT
.
21
2.2.5
RT-QPCR
.
23
2.2.6
FUNCTIONAL
ASSAYS
.
23
2.2.7
RNA
SEQUENCING
.
23
2.2.8
STATISTICS
.
24
3
RESULTS.
25
3.1
TP53
MUTATIONAL
STATUS
HAS
PROGNOSTIC
RELEVANCE
FOR
THE
RISK
OF
RELAPSE
.
25
3.2
GENOMIC
LOCALISATION
AND
ANALYSIS
OF
TP53
MUTATIONS
IN
PEDIATRIC
BURKITT
PATIENTS
.
26
3.3
ESTABLISHMENT
OF
TP53
OVEREXPRESSION
OF
POINT
MUTANTS
R175H,
R273H
AND
R273C
IN
BL-70
CELLS
27
3.3.1
VALIDATION
OF
TP53
OVEREXPRESSION
UPON
INDUCTION
WITH
DOXYCYCLINE.
29
3.3.2
OVEREXPRESSION
OF
TP53
POINT
MUTANTS
SHOW
INCREASE
IN
CELL
VIABILITY
.
29
3.4
ESTABLISHMENT
OF
A
TP53
KNOCKDOWN
IN
BL-70,
NAMALWA
AND
HELA
CELLS
.
30
3.4.1
VALIDATION
OF
TP53
KNOCKDOWN
UPON
INDUCTION
WITH
DOXYCYCLINE.
33
3.4.2
TP53
KNOCKDOWN
CELLS
SHOW
A
DECREASE
IN
CELL
VIABILITY
.
34
3.5
GENE
EXPRESSION
PROFILING
OF
TP53
KNOCKDOWN
CELLS
.
35
3.5.1
GENERAL
INFORMATION
.
35
3.5.2
GENES
UPREGULATED
TP53
KNOCKDOWN
CELLS
.
35
3.5.3
GENES
DOWNREGULATED
IN
TP53
KNOCKDOWN
CELLS
.
37
3.5.4
CLUSTER
OF
DIFFERENTIATION
MARKERS
REGULATED
IN
TP53
KNOCKDOWN
ANALYSIS
.
37
4
DISCUSSION
.
39
4.1
TP53
GOF
MUTANTS
SHOW
INCREASE
IN
CELL
VIABILITY
IN
VITRO
.
39
4.2
TP53
GOF
MUTANTS
AS
POTENTIAL
GENETIC
RISK
FACTOR
IN
PEDIATRIC
BL
.
40
4.3
H1
LINKER
HISTONE
ISOFORMS
HL-5
AND
H1-0
ARE
DIFFERENTIALLY
REGULATED
IN
TP53
GOF
CELLS
.41
4.4
CD79A
DIFFERENTIALLY
REGULATED
IN
TP53
GOF
CELLS
.
42
5
CONCLUSION
.
44
6
REFERENCES
.
45
7
ACKNOWLEDGEMENTS
.
57
8
CURRICULUM
VITAE
.
58 |
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| institution | BVB |
| language | English |
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| physical | 59 Blätter Illustrationen, Diagramme 30 cm |
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| spelling | Feldmeyer, Leon Gabriel 1998- Verfasser (DE-588)1292904593 aut Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma vorgelegt von Feldmeyer, Leon Gabriel Münster 2023 59 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Westfälische Wilhelms-Universität Münster $gBeschränkt für den Austausch (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1291583068/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034927063&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p dnb 20230824 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Feldmeyer, Leon Gabriel 1998- Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| subject_GND | (DE-588)4113937-9 |
| title | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| title_auth | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| title_exact_search | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| title_exact_search_txtP | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| title_full | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma vorgelegt von Feldmeyer, Leon Gabriel |
| title_fullStr | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma vorgelegt von Feldmeyer, Leon Gabriel |
| title_full_unstemmed | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma vorgelegt von Feldmeyer, Leon Gabriel |
| title_short | Characterising the role of TP53 in the pathogenesis of pediatric Burkitt lymphoma |
| title_sort | characterising the role of tp53 in the pathogenesis of pediatric burkitt lymphoma |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1291583068/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034927063&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT feldmeyerleongabriel characterisingtheroleoftp53inthepathogenesisofpediatricburkittlymphoma |
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