Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction:
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Ulm
2021
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | 131 Blätter Illustrationen, Diagramme 30 cm |
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MARC
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| 100 | 1 | |a Mayer, Stefanie |d 1990- |e Verfasser |0 (DE-588)1253686661 |4 aut | |
| 245 | 1 | 0 | |a Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |c Stefanie Mayer |
| 264 | 1 | |a Ulm |c 2021 | |
| 300 | |a 131 Blätter |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Universität Ulm |d 2021 | ||
| 650 | 0 | |a Chemogenomics | |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 710 | 2 | |a Universität Ulm |0 (DE-588)30607-1 |4 dgg | |
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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=034164274&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
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| 883 | 2 | |8 2\p |a dnb |d 20221212 |q DE-101 |u https://d-nb.info/provenance/plan#dnb | |
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|---|---|
| adam_text | TABLE
OF
CONTENT
1
INTRODUCTION
.................................................................................................
14
1.1
CANCER
...............................................................................................................
14
1.2
LUNG
CANCER
......................................................................................................
15
1.2.1
EPIDEMIOLOGY
OF
LUNG
CANCER
......................................................................
15
1.2.2
RISK
FACTORS
FOR
LUNG
CANCER
........................................................................
15
1.2.3
NON-SMALL
CELL
LUNG
CANCER
.........................................................................
16
1.3
PRINCIPLES
OF
THERAPY
FOR
LUNG
CANCER
................................................................
18
1.3.1
SURGERY
AND
SYSTEMIC
THERAPY
FOR
TREATMENT
OF
NSCLC
IN
EARLY
STAGES....
18
1.3.2
TARGETED
THERAPY
BY
USING
SMALL
MOLECULE
INHIBITORS
TO
TARGET
ONCOGENIC
MUTATIONS
IN
LUAD
...........................................................................
18
1.4
HETEROGENEITY
IN
NSCLC
.................................................................................
20
1.5
LIQUID
BIOPSY
TO
DECIPHER
TUMOR
HETEROGENEITY
FOR
TARGETED
THERAPY
...............
21
1.5.1
ADVANTAGES
OF
LIQUID
BIOPSY
TOWARDS
TISSUE
BIOPSY
...................................
21
1.5.2
CIRCULATING
TUMOR
DNAFOR
MUTATIONAL
GENOTYPING
IN
NSCLC
....................
23
1.6
THE
IMPORTANCE
OF
IMMUNE
CHECKPOINTS
IN
NSCLC
.........................................
24
1.6.1
CANCER
IMMUNOEDITING
TO
BYPASS
IMMUNE
SURVEILLANCE
............................
24
1.6.2
T
CELL
EXHAUSTION
........................................................................................
24
1.6.3
IMMUNE
ESCAPE
MECHANISMS
IN
CANCER
....................................................
25
1.6.4
RELEVANT
IMMUNE
CHECKPOINTS
IN
NSCLC
.................................................
25
1.6.5
IMMUNE
CHECKPOINT
INHIBITOR
THERAPY
.........................................................
26
1.7
THE
ROLE
OF
THE
NF
K
B
SIGNALING
PATHWAY
IN
CANCER
.........................................
28
1.7.1
NF
K
B
SIGNALING
PATHWAY
...........................................................................
28
1.7.2
TUMORIGENIC
EFFECT
OF
NF
K
B
BY
AFFECTING
THE
TUMOR
MICROENVIRONMENT
....30
1.7.3
THE
TUMOR
INTRINSIC
ROLE
OF
NF
K
B
...............................................................
30
1.8
AIM
OF
THE
STUDY
................................................................................................
32
2
MATERIAL
AND
METHODS
..............................................................................
33
2.1
MATERIAL
.............................................................................................................
33
2.1.1
CELL
LINES
.....................................................................................................
33
2.1.2
TISSUE
CULTURE
MEDIA
..................................................................................
33
2.1.3
ANTIBODIES
..................................................................................................
34
2.1.4
INHIBITORS
.....................................................................................................
35
2.1.5
COMMERCIAL
KITS
..........................................................................................
35
2.1.6
POLYMERASES
AND
OTHER
ENZYMES
..............................................................
36
2.1.7
OLIGONUCLEOTIDES
AND
PLASMIDS
FOR
SHRNA-MEDIATED
KNOCKDOWN
.............
36
2.1.8
BUFFERS
AND
SOLUTIONS
.................................................................................
37
2.1.9
CHEMICALS
..................................................................................................
38
2.1.10
SOFTWARE
AND
WEB-BASED
APPLICATIONS
....................................................
40
2.1.11
LABORATORY
EQUIPMENT
..............................................................................
41
2.1.12
CONSUMABLES
...........................................................................................
42
2.2
METHODS
............................................................................................................
43
2.2.1
PATIENTS
CHARACTERISTICS
OF
THE
TWO
STUDY
COHORTS
......................................
43
2.2.2
HUMAN
TISSUE
BIOPSY
..................................................................................
44
2.2.3
PLASMA
COLLECTION
FOR
CTDNA
EXTRACTION
.....................................................
44
2.2.4
DNA
EXTRACTION
FROM
FFPE
TISSUE
AND
PLASMA
SAMPLES
...........................
44
2.2.5
DNA
AND
RNA
EXTRACTION
FROM
FFPE
TISSUE
..............................................
45
2.2.6
QUANTIFICATION
OF
FFPE
DNA
AND
CTDNA
...................................................
45
2.2.7
QUANTIFICATION
OF
FFPE
RNA
......................................................................
45
2.2.8
CTDNA
PURIFICATION
PROCEDURE
....................................................................
46
2.2.9
TARGETED
AMPLICON
SEQUENCING
ON
THE
MISEQ
...........................................
46
2.2.10
TARGETED
HYBRID
CAPTURE
SEQUENCING
ON
THE
NEXTSEQ
550DX
.................
47
2.2.11
ANALYSIS
WITH
DOCKER
BASED
SOFTWARE
TRUSIGHT
ONCOLOGY
500
LOCAL
APP
V2.1
...............................................................................................
47
2.2.12
VARIANT
ANALYSIS
........................................................................................
49
2.2.13
TARGETED
RNA
SEQUENCING
ON
THE
MISEQ
USING
TRUSIGHT
RNA
PAN
CANCER
PANEL
...........................................................................................
49
2.2.14 BIOINFORMATIC
WORKFLOW
TO
DETERMINE
THE
RESPONSE
PREDICTION
SIGNATURE
.50
2.2.15
CULTIVATION
AND
HARVESTING
OF
MAMMALIAN
CELLS
.......................................
50
2.2.16
STABLE
TRANSFECTION
OF
CELLS
.......................................................................
51
2.2.17
INHIBITION
OF
CELLS
.......................................................................................
51
2.2.18
PROLIFERATION
ASSAY
...................................................................................
52
2.2.19
PREPARATION
OF
WHOLE
CELL
PROTEIN
EXTRACTS
(TNT++
EXTRACTS)
...................
52
2.2.20
DETERMINATION
OF
PROTEIN
CONCENTRATION
..................................................
52
2.2.21
IMMUNOBLOT
ANALYSIS
................................................................................
52
2.2.22
STATISTICAL
ANALYSIS
AND
DATA
VISUALIZATION
................................................
54
3.
RESULTS
...........................................................................................................
57
3.1
DECIPHERING
MUTATIONAL
LANDSCAPE
IN
NSCLC:
COMBINATORIAL
GENOTYPING
USING
DIFFERENT
BIOPSY
TYPES:
TISSUE
BIOPSY
AND
LIQUID
BIOPSY
....................................
57
3.1.1
BASELINE
CHARACTERISTICS
OF
PATIENTS
IMPLEMENTED
IN
THE
STUDY
..................
57
3.1.2
DIFFERENCES
IN
SAMPLE
HANDLING
LEADING
TO
CONTAMINATION
WITH
HIGH
MOLECULAR
GENOMIC
DNA
..................................................................
59
3.1.3
PURIFICATION
OF
CTDNA
FROM
ARCHIVED
HISTORIC
PLASMA
SAMPLES
...................
62
3.1.4
SAMPLE
PURIFICATION
INCREASES
CONCORDANCE
WITH
TISSUE
BIOPSY
IN
TARGETED
SEQUENCING
........................................................................................
66
3.2
UNRAVEL
NSCLC
TUMOR
HETEROGENEITY
AS
DRIVER
OF
THERAPY
FAILURE
TO
IMMUNE
CHECKPOINT
INHIBITOR
NIVOLUMAB
...................................................................
69
3.2.1
PATIENTS
AND
TUMOR
CHARACTERISTICS
.............................................................
69
3.2.2
OVERALL
SURVIVAL
SIGNIFICANTLY
CORRELATES
WITH
PROGRESSION
FREE
SURVIVAL
.....
71
3.2.3
DNA
SEQUENCING
UNRAVELED
DEFECTS
IN
DNA
DAMAGE
REPAIR
PATHWAYS
TO
AFFECT
RESPONSE
TO
NIVOLUMAB
...........................................................
74
3.2.4
MDM4
AND
RET
GENE
AMPLIFICATIONS
ARE
PREDICTIVE
FOR
RISK
OF
PROGRESSION
TO
NIVOLUMAB
TREATMENT
....................................................................
79
3.2.5
23
SELECTED
DIFFERENTIALLY
EXPRESSED
GENES
FOR
CLASSIFICATION
OF
THREE
RESPONSE
GROUPS
..............................................................................
80
3.3
DETERMINING
POSSIBLE
MECHANISMS
OF
IMMUNE
CHECKPOINT
PROTEIN
EXPRESSION
IN
NSCLC
CELL
LINES
..............................................................................................
88
3.3.1
IMMUNE
CHECKPOINT
PROTEIN
EXPRESSION
IS
HETEROGENEOUS
IN
NSCLC
ADENOCARCINOMA
CELL
LINES
................................................................
88
3.3.2
SHRNA-MEDIATED
KNOCK
DOWN
OF
THE
IKK
COMPLEX
COMPONENTS
IKK2
OR
NEMO
RESULTED
IN
DIMINISHED
NECTIN-2
EXPRESSION
...................................
89
4.
DISCUSSION
.....................................................................................................
92
4.1
PURIFICATION
PROCEDURE
RESCUING
NON-INFORMATIVE
CTDNA
SAMPLES
TO
DECIPHER
THE
MUTATIONAL
LANDSCAPE
IN
NSCLC
......................................................................
92
4.2
DEFINING
AN
EXPRESSION
SIGNATURE
TO
PREDICT
RESPONSE
TO
THE
IMMUNE
CHECKPOINT
INHIBITOR
NIVOLUMAB
IN
NSCLC
..........................................................................
94
4.3
NECTIN-2
EXPRESSION
AND
ITS
DEPENDENCY
OF
NF
K
B
.........................................
101
5.
SUMMARY
.......................................................................................................
104
6.
REFERENCES
.................................................................................................
106
7.
APPENDIX
.......................................................................................................
121
7.1
CONTENT
OF
TABLES
.............................................................................................
121
7.2
CONTENT
OF
FIGURES
..........................................................................................
122
4
7.3
R
SCRIPTS
...........................................................................................................
124
7.3.1
DESEQ2
.....................................................................................................
124
7.3.2
LOGCPM
.....................................................................................................
124
7.3.3
CORRELATION
PLOT
.......................................................................................
124
7.3.4
COX
REGRESSION
........................................................................................
124
7.4
LINEAR
SVM
......................................................................................................
126
7.5
RAW
DATA
CTDNA
.............................................................................................
128
7.6
GSEA
OF
THE
MUTATION
PROFILE
..........................................................................
129
5
|
| adam_txt |
TABLE
OF
CONTENT
1
INTRODUCTION
.
14
1.1
CANCER
.
14
1.2
LUNG
CANCER
.
15
1.2.1
EPIDEMIOLOGY
OF
LUNG
CANCER
.
15
1.2.2
RISK
FACTORS
FOR
LUNG
CANCER
.
15
1.2.3
NON-SMALL
CELL
LUNG
CANCER
.
16
1.3
PRINCIPLES
OF
THERAPY
FOR
LUNG
CANCER
.
18
1.3.1
SURGERY
AND
SYSTEMIC
THERAPY
FOR
TREATMENT
OF
NSCLC
IN
EARLY
STAGES.
18
1.3.2
TARGETED
THERAPY
BY
USING
SMALL
MOLECULE
INHIBITORS
TO
TARGET
ONCOGENIC
MUTATIONS
IN
LUAD
.
18
1.4
HETEROGENEITY
IN
NSCLC
.
20
1.5
LIQUID
BIOPSY
TO
DECIPHER
TUMOR
HETEROGENEITY
FOR
TARGETED
THERAPY
.
21
1.5.1
ADVANTAGES
OF
LIQUID
BIOPSY
TOWARDS
TISSUE
BIOPSY
.
21
1.5.2
CIRCULATING
TUMOR
DNAFOR
MUTATIONAL
GENOTYPING
IN
NSCLC
.
23
1.6
THE
IMPORTANCE
OF
IMMUNE
CHECKPOINTS
IN
NSCLC
.
24
1.6.1
CANCER
IMMUNOEDITING
TO
BYPASS
IMMUNE
SURVEILLANCE
.
24
1.6.2
T
CELL
EXHAUSTION
.
24
1.6.3
IMMUNE
ESCAPE
MECHANISMS
IN
CANCER
.
25
1.6.4
RELEVANT
IMMUNE
CHECKPOINTS
IN
NSCLC
.
25
1.6.5
IMMUNE
CHECKPOINT
INHIBITOR
THERAPY
.
26
1.7
THE
ROLE
OF
THE
NF
K
B
SIGNALING
PATHWAY
IN
CANCER
.
28
1.7.1
NF
K
B
SIGNALING
PATHWAY
.
28
1.7.2
TUMORIGENIC
EFFECT
OF
NF
K
B
BY
AFFECTING
THE
TUMOR
MICROENVIRONMENT
.30
1.7.3
THE
TUMOR
INTRINSIC
ROLE
OF
NF
K
B
.
30
1.8
AIM
OF
THE
STUDY
.
32
2
MATERIAL
AND
METHODS
.
33
2.1
MATERIAL
.
33
2.1.1
CELL
LINES
.
33
2.1.2
TISSUE
CULTURE
MEDIA
.
33
2.1.3
ANTIBODIES
.
34
2.1.4
INHIBITORS
.
35
2.1.5
COMMERCIAL
KITS
.
35
2.1.6
POLYMERASES
AND
OTHER
ENZYMES
.
36
2.1.7
OLIGONUCLEOTIDES
AND
PLASMIDS
FOR
SHRNA-MEDIATED
KNOCKDOWN
.
36
2.1.8
BUFFERS
AND
SOLUTIONS
.
37
2.1.9
CHEMICALS
.
38
2.1.10
SOFTWARE
AND
WEB-BASED
APPLICATIONS
.
40
2.1.11
LABORATORY
EQUIPMENT
.
41
2.1.12
CONSUMABLES
.
42
2.2
METHODS
.
43
2.2.1
PATIENTS
CHARACTERISTICS
OF
THE
TWO
STUDY
COHORTS
.
43
2.2.2
HUMAN
TISSUE
BIOPSY
.
44
2.2.3
PLASMA
COLLECTION
FOR
CTDNA
EXTRACTION
.
44
2.2.4
DNA
EXTRACTION
FROM
FFPE
TISSUE
AND
PLASMA
SAMPLES
.
44
2.2.5
DNA
AND
RNA
EXTRACTION
FROM
FFPE
TISSUE
.
45
2.2.6
QUANTIFICATION
OF
FFPE
DNA
AND
CTDNA
.
45
2.2.7
QUANTIFICATION
OF
FFPE
RNA
.
45
2.2.8
CTDNA
PURIFICATION
PROCEDURE
.
46
2.2.9
TARGETED
AMPLICON
SEQUENCING
ON
THE
MISEQ
.
46
2.2.10
TARGETED
HYBRID
CAPTURE
SEQUENCING
ON
THE
NEXTSEQ
550DX
.
47
2.2.11
ANALYSIS
WITH
DOCKER
BASED
SOFTWARE
TRUSIGHT
ONCOLOGY
500
LOCAL
APP
V2.1
.
47
2.2.12
VARIANT
ANALYSIS
.
49
2.2.13
TARGETED
RNA
SEQUENCING
ON
THE
MISEQ
USING
TRUSIGHT
RNA
PAN
CANCER
PANEL
.
49
2.2.14 BIOINFORMATIC
WORKFLOW
TO
DETERMINE
THE
RESPONSE
PREDICTION
SIGNATURE
.50
2.2.15
CULTIVATION
AND
HARVESTING
OF
MAMMALIAN
CELLS
.
50
2.2.16
STABLE
TRANSFECTION
OF
CELLS
.
51
2.2.17
INHIBITION
OF
CELLS
.
51
2.2.18
PROLIFERATION
ASSAY
.
52
2.2.19
PREPARATION
OF
WHOLE
CELL
PROTEIN
EXTRACTS
(TNT++
EXTRACTS)
.
52
2.2.20
DETERMINATION
OF
PROTEIN
CONCENTRATION
.
52
2.2.21
IMMUNOBLOT
ANALYSIS
.
52
2.2.22
STATISTICAL
ANALYSIS
AND
DATA
VISUALIZATION
.
54
3.
RESULTS
.
57
3.1
DECIPHERING
MUTATIONAL
LANDSCAPE
IN
NSCLC:
COMBINATORIAL
GENOTYPING
USING
DIFFERENT
BIOPSY
TYPES:
TISSUE
BIOPSY
AND
LIQUID
BIOPSY
.
57
3.1.1
BASELINE
CHARACTERISTICS
OF
PATIENTS
IMPLEMENTED
IN
THE
STUDY
.
57
3.1.2
DIFFERENCES
IN
SAMPLE
HANDLING
LEADING
TO
CONTAMINATION
WITH
HIGH
MOLECULAR
GENOMIC
DNA
.
59
3.1.3
PURIFICATION
OF
CTDNA
FROM
ARCHIVED
HISTORIC
PLASMA
SAMPLES
.
62
3.1.4
SAMPLE
PURIFICATION
INCREASES
CONCORDANCE
WITH
TISSUE
BIOPSY
IN
TARGETED
SEQUENCING
.
66
3.2
UNRAVEL
NSCLC
TUMOR
HETEROGENEITY
AS
DRIVER
OF
THERAPY
FAILURE
TO
IMMUNE
CHECKPOINT
INHIBITOR
NIVOLUMAB
.
69
3.2.1
PATIENTS
AND
TUMOR
CHARACTERISTICS
.
69
3.2.2
OVERALL
SURVIVAL
SIGNIFICANTLY
CORRELATES
WITH
PROGRESSION
FREE
SURVIVAL
.
71
3.2.3
DNA
SEQUENCING
UNRAVELED
DEFECTS
IN
DNA
DAMAGE
REPAIR
PATHWAYS
TO
AFFECT
RESPONSE
TO
NIVOLUMAB
.
74
3.2.4
MDM4
AND
RET
GENE
AMPLIFICATIONS
ARE
PREDICTIVE
FOR
RISK
OF
PROGRESSION
TO
NIVOLUMAB
TREATMENT
.
79
3.2.5
23
SELECTED
DIFFERENTIALLY
EXPRESSED
GENES
FOR
CLASSIFICATION
OF
THREE
RESPONSE
GROUPS
.
80
3.3
DETERMINING
POSSIBLE
MECHANISMS
OF
IMMUNE
CHECKPOINT
PROTEIN
EXPRESSION
IN
NSCLC
CELL
LINES
.
88
3.3.1
IMMUNE
CHECKPOINT
PROTEIN
EXPRESSION
IS
HETEROGENEOUS
IN
NSCLC
ADENOCARCINOMA
CELL
LINES
.
88
3.3.2
SHRNA-MEDIATED
KNOCK
DOWN
OF
THE
IKK
COMPLEX
COMPONENTS
IKK2
OR
NEMO
RESULTED
IN
DIMINISHED
NECTIN-2
EXPRESSION
.
89
4.
DISCUSSION
.
92
4.1
PURIFICATION
PROCEDURE
RESCUING
NON-INFORMATIVE
CTDNA
SAMPLES
TO
DECIPHER
THE
MUTATIONAL
LANDSCAPE
IN
NSCLC
.
92
4.2
DEFINING
AN
EXPRESSION
SIGNATURE
TO
PREDICT
RESPONSE
TO
THE
IMMUNE
CHECKPOINT
INHIBITOR
NIVOLUMAB
IN
NSCLC
.
94
4.3
NECTIN-2
EXPRESSION
AND
ITS
DEPENDENCY
OF
NF
K
B
.
101
5.
SUMMARY
.
104
6.
REFERENCES
.
106
7.
APPENDIX
.
121
7.1
CONTENT
OF
TABLES
.
121
7.2
CONTENT
OF
FIGURES
.
122
4
7.3
R
SCRIPTS
.
124
7.3.1
DESEQ2
.
124
7.3.2
LOGCPM
.
124
7.3.3
CORRELATION
PLOT
.
124
7.3.4
COX
REGRESSION
.
124
7.4
LINEAR
SVM
.
126
7.5
RAW
DATA
CTDNA
.
128
7.6
GSEA
OF
THE
MUTATION
PROFILE
.
129
5 |
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| any_adam_object_boolean | 1 |
| author | Mayer, Stefanie 1990- |
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| bvnumber | BV048899844 |
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| format | Thesis Book |
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| id | DE-604.BV048899844 |
| illustrated | Illustrated |
| index_date | 2024-07-03T21:50:38Z |
| indexdate | 2024-07-10T09:49:16Z |
| institution | BVB |
| institution_GND | (DE-588)30607-1 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034164274 |
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| physical | 131 Blätter Illustrationen, Diagramme 30 cm |
| publishDate | 2021 |
| publishDateSearch | 2021 |
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| spelling | Mayer, Stefanie 1990- Verfasser (DE-588)1253686661 aut Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction Stefanie Mayer Ulm 2021 131 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Universität Ulm 2021 Chemogenomics (DE-588)4113937-9 Hochschulschrift gnd-content Universität Ulm (DE-588)30607-1 dgg B:DE-101 application/pdf https://d-nb.info/1265028907/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034164274&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p emakn 0,97865 20221209 DE-101 https://d-nb.info/provenance/plan#emakn 2\p dnb 20221212 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Mayer, Stefanie 1990- Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction Chemogenomics |
| subject_GND | (DE-588)4113937-9 |
| title | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |
| title_auth | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |
| title_exact_search | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |
| title_exact_search_txtP | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |
| title_full | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction Stefanie Mayer |
| title_fullStr | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction Stefanie Mayer |
| title_full_unstemmed | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction Stefanie Mayer |
| title_short | Deciphering tumor heterogeneity in non-small cell lung cancer to define therapy prediction |
| title_sort | deciphering tumor heterogeneity in non small cell lung cancer to define therapy prediction |
| topic | Chemogenomics |
| topic_facet | Chemogenomics Hochschulschrift |
| url | https://d-nb.info/1265028907/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034164274&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT mayerstefanie decipheringtumorheterogeneityinnonsmallcelllungcancertodefinetherapyprediction AT universitatulm decipheringtumorheterogeneityinnonsmallcelllungcancertodefinetherapyprediction |
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Indexes