Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model:
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2020
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| 100 | 1 | |a Siebert, Susann |d 1987- |e Verfasser |0 (DE-588)1220732117 |4 aut | |
| 245 | 1 | 0 | |a Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |c vorgelegt von Susann Siebert |
| 264 | 1 | |a Köln |c 2020 | |
| 300 | |a 128, XXXV Seiten, Seite VI-XXI |b Illustrationen |c 21 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Universität zu Köln |d 2020 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032653659&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
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| 883 | 1 | |8 1\p |a adb |d 20201013 |q DE-101 |u https://d-nb.info/provenance/plan#adb | |
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| adam_text | TABLE
OF
CONTENT
ACKNOWLEDGEMENT
.........................................................................................................................
I
ZUSAMMENFASSUNG
......................................................................................................................
ILL
ABSTRACT
..........................................................................................................................................
V
TABLE
OF
CONTENT
...........................................................................................................................
VI
ABBREVIATIONS
...............................................................................................................................
X
1
INTRODUCTION
................................................................................................................................
1
1.1
THE
HALLMARKS
OF
CANCER
...................................................................................................
1
1.2
CANCER
PREDISPOSITION
SYNDROMES
................................................................................2
1.3
LYNCH
SYNDROME/HNPCC
.................................................................................................
4
1.3.1
MOLECULAR
BASIS
OF
LYNCH
SYNDROME
..........................................................................
5
1.3.2
DIAGNOSIS
AND
TESTING
OF
LYNCH
SYNDROME
PATIENTS
..................................................
6
1.3.3
THERAPY
APPROACHES
FOR
LYNCH
SYNDROME
CANCERS
................................................
10
1.4
THE
DNA
MISMATCH
REPAIR
(MMR)
SYSTEM
.................................................................
11
1.4.1
ALTERNATIVE
FUNCTIONS
OF
THE
MMR
SYSTEM
................................................................
13
1.5
EPIGENETICS
........................................................................................................................16
1.5.1
EPIGENETICS
AND
DNA
REPAIR
.....................................................................................
20
1.6
AIM
OF
THE
WORK
................................................................................................................
23
2
RESULTS
.......................................................................................................................................
24
2.1
IDENTIFICATION
OF
MUTATED
HOTSPOT*
REGIONS
IN
HNPCC-RELATED
TUMORS
.............
24
2.2
IDENTIFICATION
OF
HOTSPOT*
REGIONS
IN
LS
TUMORS
......................................................
26
2.3
CHARACTERIZATION
OF
HOTSPOTS*
......................................................................................
27
2.3.1
MUTATION
SPECTRUM
ANALYSIS
OF
IDENTIFIED
HOTSPOTS
................................................
27
2.3.2
MOTIF
ANALYSIS
AT
HOTSPOT
MUTATIONS
........................................................................
29
2.3.3
HOTSPOTS
AND
GENE
EXPRESSION
...............................................................................
30
2.3.4
PATHWAY
ANALYSIS
OF
IDENTIFIED
HOTSPOTS
.................................................................
31
2.3.5
COMPARISON
OF
IDENTIFIED
HOTSPOTS
WITH
OTHER
CANCER
HOTSPOT
DATA
.................
35
2.4
VALIDATION
AND
FURTHER
ANALYSIS
OF
HOTSPOTS*
IN
LS
ASSOCIATED
TUMORS
............
36
2.4.1
INFLUENCE
OF
THE
TYPE
OF
MMR
DEFICIENCY
ON
THE
HOTSPOT
MUTATION
SPECIMEN
...
38
2.4.1.1
IMPACT
OF
THE
MUTATED
MMR
PROTEIN
ON
THE
NUMBER
OF HOTSPOT
MUTATIONS
39
2.4.1.2
IMPACT
OF
DIFFERENT
MMR
PROTEIN
STATES
ON
THE
OCCURRENCE
OF
HOTSPOT
MUTATIONS
...........................................................................................................................
41
2.4.1.3
IMPACT
OF
DIFFERENT
MMR
PROTEIN
STATES
ON
THE
MUTATION
SPECTRUM
IN
HOTSPOT
REGIONS
...............................................................................................................................
42
2.5
COMPARISON
OF
HOTSPOT*
MUTATIONS
IN
MICROSATELLITE
INSTABLE
LS
TUMORS
AND
SPORADIC
TUMORS
......................................................................................................................
44
2.6
SELECTION
OF
HOTSPOT*
CANDIDATE
GENES
FOR
FUNCTIONAL
ANALYSIS
..........................
46
TABLE
OF
CONTENT
2.6.1
NEDD9
AS
A
CANDIDATE
FOR
FUNCTIONAL
ANALYSIS
.....................................................
48
2.6.1.1
INFLUENCE
OF
THE
MUTATION
A728T
ON
MIGRATION
BEHAVIOUR
OF
MCF-7
CELLS...
51
2.6.1.2
INFLUENCE
OF
THE
MUTATION
A728T
ON
VIABILITY
OF
MCF-7
CELLS
........................52
2.6.1.3
INFLUENCE
OF
THE
MUTATION
A728T
ON
CASPASE3/7
ACTIVITY
OF
MCF-7
CELLS
....
53
2.7
EPIGENETIC
ALTERATIONS
IN
AN
MSH2
MOUSE
MODEL
................................................
55
2.7.1
IRRADIATION
OF
MMR-DEFICIENT
AND
-PROFICIENT
MICE
.................................................
55
2.7.2
CHLP-SEQ
ANALYSIS
OF
INTESTINE
TISSUES
OF
MICE
WITH
DIFFERENT
GENOTYPES
AND
RADIATION
TREATMENTS
..........................................................................................................
57
2.7.3
H3K36ME3
HISTONE
METHYLATION
IS
ELEVATED
IN
MSH2
+/
AND
MSHZ
7
MICE
...........
59
2.7.4
HISTONE
METHYLATION
SIGNATURES
CORRELATE
WITH
GENE
EXPRESSION
LEVELS
..............
60
2.7.5
HISTONE
METHYLATION
SIGNATURES
ARE
DIFFERENT
IN
MSH2
+/
AND
MSH2
/
MICE
..........
61
2.7.6
CHANGES
IN
HISTONE
METHYLATION
SIGNATURES
AFTER
A
SINGLE
RADIATION
HIT
...............
64
2.7.7
A
SIMILAR
EPIGENETIC
RESPONSE
IS
INDUCED
BY
RADIATION
AND
MSH2
KNOCKOUT
......
65
2.7.8
FUNCTIONAL
ANNOTATION
OF
THE
COMMON
EPIGENETIC
RESPONSE
................................
67
3.
DISCUSSION
.............................................................................................................................
70
3.1
IDENTIFIED
HOTSPOT*
REGIONS
AND
MUTATIONS
IN
HNPCC
TUMORS
............................
70
3.2
FIRST
INSIGHTS
INTO
THE
FUNCTIONAL
IMPACT
OF
IDENTIFIED
HOTSPOT*
MUTATIONS
......
74
3.3
HOTSPOT*
REGIONS
IN
HNPCC
AND
SPORADIC
CRC
-
A
COMPARISON
........................
75
3.4
MSH2
DEFICIENT
CELLS
DISPLAY
EPIGENOME-WIDE
ALTERATIONS
IN
H3K4ME3,
H3K27ME3
AND
H3K36ME3
PATTERNS
................................................................................
76
3.5
EPIGENETIC
PROFILES
IN
MSH2
DEFICIENT
CELLS
AND
AFTER
A
SINGLE
HIT
IRRADIATION
ARE
HIGHLY
SIMILAR
.........................................................................................................................
79
3.6
ADAPTED
MODEL
FOR
HNPCC
INCLUDING
GENETIC
AND
EPIGENETIC
ALTERATIONS
........
81
3.7
CONCLUSION
AND
OUTLOOK
................................................................................................
83
4
MATERIAL
AND
METHODS
...........................................................................................................
85
4.1
METHODS
........................................................................................................................
85
4.1.1
MOLECULAR
BIOLOGICAL
METHODS
..............................................................................
85
4.1.1.1
POLYMERASE
CHAIN
REACTION
(PCR)
....................................................................
85
4.1.1.2
SITE-DIRECTED
MUTAGENESIS
(SDM)
....................................................................
86
4.1.1.3
AGAROSE
GEL
ELECTROPHORESIS
..............................................................................
87
4.1.1.4
DNA-PURIFICATIONS
...............................................................................................
88
4.1.1.4.1
PURIFICATION
OF
PCR-PRODUCTS
.....................................................................
88
4.1.1.4.2
PURIFICATION
OF
DNA
FROM
AGAROSE-GELS
.....................................................88
4.1.1.4.3
PLASMID
DNA
EXTRACTIONS
............................................................................
89
4.1.1.4.3.1
MINIPREP
................................................................................................
89
4.1.1.4.3.2
MAXIPREP
...............................................................................................
89
4.1.1.5
DNA
AND
RNA
CONCENTRATION
MEASUREMENT
...................................................
90
4.1.1.5.1
NANODROP*
.................................................................................................
90
4.1.1.5.2
QUBIT
ASSAY
..................................................................................................
91
VII
TABLE
OF
CONTENT
4.1.1.6
RESTRICTION
ENZYME
DIGEST
..................................................................................
91
4.1.1.7
LIGATION
.................................................................................................................
91
4.1.1.8
QUANTITATIVE
PCR
................................................................................................
92
4.1.2
MICROBIOLOGICAL
METHODS
............................................................................................
92
4.1.2.1
MEDIA
.....................................................................................................................
92
4.1.2.2
E.
COLI
STRAINS
........................................................................................................
93
4.1.2.3
TRANSFORMATION
OF
E.
COLI
CELLS
............................................................................
93
4.1.3
PROTEIN
CHEMICAL
METHODS
.........................................................................................
94
4.1.3.1
PROTEIN
EXTRACTION
FROM
MAMMALIAN
CELLS
........................................................
94
4.1.3.2
PROTEIN
QUANTIFICATION
..........................................................................................
94
4.1.3.3SDS-
PAGE
..........................................................................................................
95
4.1.3.4
WESTERN
BLOTTING
AND
IMMUNOSTAINING
OF
PROTEINS
..........................................
95
4.1.3.5
CHROMATIN
IMMUNOPRECIPITATION
(CHIP)
............................................................
96
4.1.4
CELL-BIOLOGICAL
METHODS
..............................................................................................
97
4.1.4.1
HUMAN
CELL
LINE
....................................................................................................
97
4.1.4.2
CRYO-PRESERVATION
OF
HUMAN
CELL
LINE
................................................................
98
4.1.4.3
THAWING
AND
CULTIVATION
OF
HUMAN
CELL
LINE
.....................................................
98
4.1.4.4
TRANSFECTION
OF
CELLS
............................................................................................
98
4.1.4.5
CELL
VIABILITY
ASSAY
...............................................................................................
99
4.1.4.6
CASPASE
3/7
ACTIVITY
ASSAY
..............................................................................
100
4.1.4.7
SCRATCH
ASSAY
.....................................................................................................
100
4.1.5
DNA
SEQUENCING
METHODS
.......................................................................................
101
4.1.5.1
SANGER
SEQUENCING
...........................................................................................
101
4.1.5.2
NEXT
GENERATION
SEQUENCING
METHODS
(NGS)
................................................
101
4.1.5.2.1
TARGETED
HOTSPOT
AMPLICON
SEQUENCING
................................................
101
4.1.5.2.2
CHROMATIN
IMMUNOPRECIPITATION
DNA-SEQUENCING
(CHLP-SEQ)
..........
103
4.1.6
BIOINFORMATICAL
ANALYSIS
...........................................................................................103
4.1.6.1
PROCESSING
OF
RAW
DATA
.....................................................................................103
4.1.6.1.1
PROCESSING
OF
TARGETED
HOTSPOT
AMPLICON
SEQUENCING
READS
............103
4.1.6.1.2
PROCESSING
OFCHIP
SEQ
READS
.................................................................104
4.1.6.2
PATHWAY
ANALYSES
.............................................................................................104
4.1.6.3
DNA
MOTIF
ANALYSIS
............................................................................................
105
4.2
MATERIAL
........................................................................................................................
105
4.2.1
STANDARD
EQUIPMENT
................................................................................................
105
4.2.2
MOLECULAR
BIOLOGICAL
EQUIPMENT
..............................................................................106
4.2.2.1
OLIGONUCLEOTIDES
.............................................................................................
106
4.2.3
MICROBIOLOGICAL
EQUIPMENT
.......................................................................................108
4.2.4
PROTEIN
CHEMICAL
EQUIPMENT
...................................................................................108
4.2.5
ANTIBODIES
..................................................................................................................109
VIII
TABLE
OF
CONTENT
4.2.5.1
PRIMARY
ANTIBODIES
............................................................................................109
4.2.5.2
SECONDARY
ANTIBODIES
......................................................................................
109
4.2.6
CELL-BIOLOGICAL
EQUIPMENT
.......................................................................................110
4.2.7
DNA
SEQUENCING
EQUIPMENT
..................................................................................110
4.2.8
VECTOR
CARDS
.............................................................................................................
111
4.2.9
PATIENT
SAMPLES
.......................................................................................................
112
4.2.10
MOUSE
SAMPLES
.....................................................................................................113
5.
REFERENCES
..........................................................................................................................
114
6.
SUPPLEMENT
..........................................................................................................................
XIII
6.1
SUPPLEMENTARY
FIGURES
................................................................................................
XIII
6.2
SUPPLEMENTARY
TABLES
................................................................................................
XVII
ERKLARUNG
................................................................................................................................
XVIII
TEILPUBLIKATIONEN
..................................................................................................................
XVIII
CURRICULUM
VITAE
.....................................................................................................................
XIX
IX
|
| adam_txt |
TABLE
OF
CONTENT
ACKNOWLEDGEMENT
.
I
ZUSAMMENFASSUNG
.
ILL
ABSTRACT
.
V
TABLE
OF
CONTENT
.
VI
ABBREVIATIONS
.
X
1
INTRODUCTION
.
1
1.1
THE
HALLMARKS
OF
CANCER
.
1
1.2
CANCER
PREDISPOSITION
SYNDROMES
.2
1.3
LYNCH
SYNDROME/HNPCC
.
4
1.3.1
MOLECULAR
BASIS
OF
LYNCH
SYNDROME
.
5
1.3.2
DIAGNOSIS
AND
TESTING
OF
LYNCH
SYNDROME
PATIENTS
.
6
1.3.3
THERAPY
APPROACHES
FOR
LYNCH
SYNDROME
CANCERS
.
10
1.4
THE
DNA
MISMATCH
REPAIR
(MMR)
SYSTEM
.
11
1.4.1
ALTERNATIVE
FUNCTIONS
OF
THE
MMR
SYSTEM
.
13
1.5
EPIGENETICS
.16
1.5.1
EPIGENETICS
AND
DNA
REPAIR
.
20
1.6
AIM
OF
THE
WORK
.
23
2
RESULTS
.
24
2.1
IDENTIFICATION
OF
MUTATED
'HOTSPOT*
REGIONS
IN
HNPCC-RELATED
TUMORS
.
24
2.2
IDENTIFICATION
OF
'HOTSPOT*
REGIONS
IN
LS
TUMORS
.
26
2.3
CHARACTERIZATION
OF
'HOTSPOTS*
.
27
2.3.1
MUTATION
SPECTRUM
ANALYSIS
OF
IDENTIFIED
'HOTSPOTS'
.
27
2.3.2
MOTIF
ANALYSIS
AT
'HOTSPOT'
MUTATIONS
.
29
2.3.3
'HOTSPOTS'
AND
GENE
EXPRESSION
.
30
2.3.4
PATHWAY
ANALYSIS
OF
IDENTIFIED
'HOTSPOTS'
.
31
2.3.5
COMPARISON
OF
IDENTIFIED
'HOTSPOTS'
WITH
OTHER
CANCER
'HOTSPOT'
DATA
.
35
2.4
VALIDATION
AND
FURTHER
ANALYSIS
OF
'HOTSPOTS*
IN
LS
ASSOCIATED
TUMORS
.
36
2.4.1
INFLUENCE
OF
THE
TYPE
OF
MMR
DEFICIENCY
ON
THE
'HOTSPOT'
MUTATION
SPECIMEN
.
38
2.4.1.1
IMPACT
OF
THE
MUTATED
MMR
PROTEIN
ON
THE
NUMBER
OF'HOTSPOT'
MUTATIONS
39
2.4.1.2
IMPACT
OF
DIFFERENT
MMR
PROTEIN
STATES
ON
THE
OCCURRENCE
OF
'HOTSPOT'
MUTATIONS
.
41
2.4.1.3
IMPACT
OF
DIFFERENT
MMR
PROTEIN
STATES
ON
THE
MUTATION
SPECTRUM
IN
'HOTSPOT'
REGIONS
.
42
2.5
COMPARISON
OF
'HOTSPOT*
MUTATIONS
IN
MICROSATELLITE
INSTABLE
LS
TUMORS
AND
SPORADIC
TUMORS
.
44
2.6
SELECTION
OF
'HOTSPOT*
CANDIDATE
GENES
FOR
FUNCTIONAL
ANALYSIS
.
46
TABLE
OF
CONTENT
2.6.1
NEDD9
AS
A
CANDIDATE
FOR
FUNCTIONAL
ANALYSIS
.
48
2.6.1.1
INFLUENCE
OF
THE
MUTATION
A728T
ON
MIGRATION
BEHAVIOUR
OF
MCF-7
CELLS.
51
2.6.1.2
INFLUENCE
OF
THE
MUTATION
A728T
ON
VIABILITY
OF
MCF-7
CELLS
.52
2.6.1.3
INFLUENCE
OF
THE
MUTATION
A728T
ON
CASPASE3/7
ACTIVITY
OF
MCF-7
CELLS
.
53
2.7
EPIGENETIC
ALTERATIONS
IN
AN
MSH2
MOUSE
MODEL
.
55
2.7.1
IRRADIATION
OF
MMR-DEFICIENT
AND
-PROFICIENT
MICE
.
55
2.7.2
CHLP-SEQ
ANALYSIS
OF
INTESTINE
TISSUES
OF
MICE
WITH
DIFFERENT
GENOTYPES
AND
RADIATION
TREATMENTS
.
57
2.7.3
H3K36ME3
HISTONE
METHYLATION
IS
ELEVATED
IN
MSH2
+/
'
AND
MSHZ
7
'
MICE
.
59
2.7.4
HISTONE
METHYLATION
SIGNATURES
CORRELATE
WITH
GENE
EXPRESSION
LEVELS
.
60
2.7.5
HISTONE
METHYLATION
SIGNATURES
ARE
DIFFERENT
IN
MSH2
+/
'
AND
MSH2'
/
'
MICE
.
61
2.7.6
CHANGES
IN
HISTONE
METHYLATION
SIGNATURES
AFTER
A
SINGLE
RADIATION
HIT
.
64
2.7.7
A
SIMILAR
EPIGENETIC
RESPONSE
IS
INDUCED
BY
RADIATION
AND
MSH2
KNOCKOUT
.
65
2.7.8
FUNCTIONAL
ANNOTATION
OF
THE
COMMON
EPIGENETIC
RESPONSE
.
67
3.
DISCUSSION
.
70
3.1
IDENTIFIED
'HOTSPOT*
REGIONS
AND
MUTATIONS
IN
HNPCC
TUMORS
.
70
3.2
FIRST
INSIGHTS
INTO
THE
FUNCTIONAL
IMPACT
OF
IDENTIFIED
'HOTSPOT*
MUTATIONS
.
74
3.3
'HOTSPOT*
REGIONS
IN
HNPCC
AND
SPORADIC
CRC
-
A
COMPARISON
.
75
3.4
MSH2
DEFICIENT
CELLS
DISPLAY
EPIGENOME-WIDE
ALTERATIONS
IN
H3K4ME3,
H3K27ME3
AND
H3K36ME3
PATTERNS
.
76
3.5
EPIGENETIC
PROFILES
IN
MSH2
DEFICIENT
CELLS
AND
AFTER
A
SINGLE
HIT
IRRADIATION
ARE
HIGHLY
SIMILAR
.
79
3.6
ADAPTED
MODEL
FOR
HNPCC
INCLUDING
GENETIC
AND
EPIGENETIC
ALTERATIONS
.
81
3.7
CONCLUSION
AND
OUTLOOK
.
83
4
MATERIAL
AND
METHODS
.
85
4.1
METHODS
.
85
4.1.1
MOLECULAR
BIOLOGICAL
METHODS
.
85
4.1.1.1
POLYMERASE
CHAIN
REACTION
(PCR)
.
85
4.1.1.2
SITE-DIRECTED
MUTAGENESIS
(SDM)
.
86
4.1.1.3
AGAROSE
GEL
ELECTROPHORESIS
.
87
4.1.1.4
DNA-PURIFICATIONS
.
88
4.1.1.4.1
PURIFICATION
OF
PCR-PRODUCTS
.
88
4.1.1.4.2
PURIFICATION
OF
DNA
FROM
AGAROSE-GELS
.88
4.1.1.4.3
PLASMID
DNA
EXTRACTIONS
.
89
4.1.1.4.3.1
MINIPREP
.
89
4.1.1.4.3.2
MAXIPREP
.
89
4.1.1.5
DNA
AND
RNA
CONCENTRATION
MEASUREMENT
.
90
4.1.1.5.1
NANODROP*
.
90
4.1.1.5.2
QUBIT
ASSAY
.
91
VII
TABLE
OF
CONTENT
4.1.1.6
RESTRICTION
ENZYME
DIGEST
.
91
4.1.1.7
LIGATION
.
91
4.1.1.8
QUANTITATIVE
PCR
.
92
4.1.2
MICROBIOLOGICAL
METHODS
.
92
4.1.2.1
MEDIA
.
92
4.1.2.2
E.
COLI
STRAINS
.
93
4.1.2.3
TRANSFORMATION
OF
E.
COLI
CELLS
.
93
4.1.3
PROTEIN
CHEMICAL
METHODS
.
94
4.1.3.1
PROTEIN
EXTRACTION
FROM
MAMMALIAN
CELLS
.
94
4.1.3.2
PROTEIN
QUANTIFICATION
.
94
4.1.3.3SDS-
PAGE
.
95
4.1.3.4
WESTERN
BLOTTING
AND
IMMUNOSTAINING
OF
PROTEINS
.
95
4.1.3.5
CHROMATIN
IMMUNOPRECIPITATION
(CHIP)
.
96
4.1.4
CELL-BIOLOGICAL
METHODS
.
97
4.1.4.1
HUMAN
CELL
LINE
.
97
4.1.4.2
CRYO-PRESERVATION
OF
HUMAN
CELL
LINE
.
98
4.1.4.3
THAWING
AND
CULTIVATION
OF
HUMAN
CELL
LINE
.
98
4.1.4.4
TRANSFECTION
OF
CELLS
.
98
4.1.4.5
CELL
VIABILITY
ASSAY
.
99
4.1.4.6
CASPASE
3/7
ACTIVITY
ASSAY
.
100
4.1.4.7
SCRATCH
ASSAY
.
100
4.1.5
DNA
SEQUENCING
METHODS
.
101
4.1.5.1
SANGER
SEQUENCING
.
101
4.1.5.2
NEXT
GENERATION
SEQUENCING
METHODS
(NGS)
.
101
4.1.5.2.1
TARGETED
'HOTSPOT'
AMPLICON
SEQUENCING
.
101
4.1.5.2.2
CHROMATIN
IMMUNOPRECIPITATION
DNA-SEQUENCING
(CHLP-SEQ)
.
103
4.1.6
BIOINFORMATICAL
ANALYSIS
.103
4.1.6.1
PROCESSING
OF
RAW
DATA
.103
4.1.6.1.1
PROCESSING
OF
TARGETED
'HOTSPOT'
AMPLICON
SEQUENCING
READS
.103
4.1.6.1.2
PROCESSING
OFCHIP
SEQ
READS
.104
4.1.6.2
PATHWAY
ANALYSES
.104
4.1.6.3
DNA
MOTIF
ANALYSIS
.
105
4.2
MATERIAL
.
105
4.2.1
STANDARD
EQUIPMENT
.
105
4.2.2
MOLECULAR
BIOLOGICAL
EQUIPMENT
.106
4.2.2.1
OLIGONUCLEOTIDES
.
106
4.2.3
MICROBIOLOGICAL
EQUIPMENT
.108
4.2.4
PROTEIN
CHEMICAL
EQUIPMENT
.108
4.2.5
ANTIBODIES
.109
VIII
TABLE
OF
CONTENT
4.2.5.1
PRIMARY
ANTIBODIES
.109
4.2.5.2
SECONDARY
ANTIBODIES
.
109
4.2.6
CELL-BIOLOGICAL
EQUIPMENT
.110
4.2.7
DNA
SEQUENCING
EQUIPMENT
.110
4.2.8
VECTOR
CARDS
.
111
4.2.9
PATIENT
SAMPLES
.
112
4.2.10
MOUSE
SAMPLES
.113
5.
REFERENCES
.
114
6.
SUPPLEMENT
.
XIII
6.1
SUPPLEMENTARY
FIGURES
.
XIII
6.2
SUPPLEMENTARY
TABLES
.
XVII
ERKLARUNG
.
XVIII
TEILPUBLIKATIONEN
.
XVIII
CURRICULUM
VITAE
.
XIX
IX |
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| author | Siebert, Susann 1987- |
| author_GND | (DE-588)1220732117 |
| author_facet | Siebert, Susann 1987- |
| author_role | aut |
| author_sort | Siebert, Susann 1987- |
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| building | Verbundindex |
| bvnumber | BV047249546 |
| ctrlnum | (OCoLC)1249683172 (DE-599)DNB1228120250 |
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| id | DE-604.BV047249546 |
| illustrated | Illustrated |
| index_date | 2024-07-03T17:07:16Z |
| indexdate | 2024-07-10T09:06:49Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032653659 |
| oclc_num | 1249683172 |
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| physical | 128, XXXV Seiten, Seite VI-XXI Illustrationen 21 cm |
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| spelling | Siebert, Susann 1987- Verfasser (DE-588)1220732117 aut Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model vorgelegt von Susann Siebert Köln 2020 128, XXXV Seiten, Seite VI-XXI Illustrationen 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Universität zu Köln 2020 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1228120250/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032653659&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p adb 20201013 DE-101 https://d-nb.info/provenance/plan#adb |
| spellingShingle | Siebert, Susann 1987- Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| subject_GND | (DE-588)4113937-9 |
| title | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| title_auth | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| title_exact_search | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| title_exact_search_txtP | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| title_full | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model vorgelegt von Susann Siebert |
| title_fullStr | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model vorgelegt von Susann Siebert |
| title_full_unstemmed | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model vorgelegt von Susann Siebert |
| title_short | Genetic and epigenetic alterations in mismatch repair deficient cells on the basis of Lynch syndrome patients and an Msh2 knockout mouse model |
| title_sort | genetic and epigenetic alterations in mismatch repair deficient cells on the basis of lynch syndrome patients and an msh2 knockout mouse model |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1228120250/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032653659&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT siebertsusann geneticandepigeneticalterationsinmismatchrepairdeficientcellsonthebasisoflynchsyndromepatientsandanmsh2knockoutmousemodel |
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