Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma:
Gespeichert in:
1. Verfasser: | |
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Format: | Abschlussarbeit Buch |
Sprache: | English |
Veröffentlicht: |
2001
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Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | IV, 189 S. Ill., graph. Darst. |
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040 | |a DE-604 |b ger |e rakwb | ||
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049 | |a DE-19 |a DE-12 |a DE-355 |a DE-188 | ||
100 | 1 | |a Kuosaite, Virginija |d 1963- |e Verfasser |0 (DE-588)123559820 |4 aut | |
245 | 1 | 0 | |a Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma |c Virginija Kuosaite |
264 | 1 | |c 2001 | |
300 | |a IV, 189 S. |b Ill., graph. Darst. | ||
336 | |b txt |2 rdacontent | ||
337 | |b n |2 rdamedia | ||
338 | |b nc |2 rdacarrier | ||
502 | |a München, Univ., Diss., 2001 | ||
650 | 0 | 7 | |a Maus |0 (DE-588)4169148-9 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Allel |0 (DE-588)4271150-2 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Osteosarkom |0 (DE-588)4172929-8 |2 gnd |9 rswk-swf |
655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
689 | 0 | 0 | |a Maus |0 (DE-588)4169148-9 |D s |
689 | 0 | 1 | |a Osteosarkom |0 (DE-588)4172929-8 |D s |
689 | 0 | 2 | |a Allel |0 (DE-588)4271150-2 |D s |
689 | 0 | |5 DE-604 | |
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943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-009690411 |
Datensatz im Suchindex
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adam_text |
OUTLINE
1.
INTRODUCTION
1
1.1.
MOLECULAR
MECHANISMS
OF
SPONTANEOUS
AND
A-RADIATION
INDUCED
OSTEOSARCOMAGENESIS
ARE
UNCLEAR
1
1.2.
OSTEOSARCOMA
IN
THE
MOUSE
2
1.2.1.
OSTEOSARCOMA
INCIDENCE
IN
THE
MOUSE
2
1.2.2.
OSTEOSARCOMA
IN
THE
MOUSE
CLOSELY
RESEMBLES
HUMAN
OSTEOSARCOMA
2
1.3.
OSTEOSARCOMA
IN
MAN
5
1.3.1.
OSTEOSARCOMA
INCIDENCE
IN
MAN
5
1.3.2.
ETIOLOGY
AND
PREDISPOSITION
TO
OSTEOSARCOMA
IN
MAN
5
1.4.
PROGRESSIVE
LOSS
OF
HETEROZYGOSITY
AND
ALLELIC
IMBALANCE
LEADS
TO
CARCINOGENESIS
9
1.5.
GENETICS
OF
HUMAN
OSTEOSARCOMA
14
1.6.
LOSS
OF
HETEROZYGOSITY
AND
ALLELIC
IMBALANCE
(LOH/AI)
STUDIES
IN
HUMAN
AND
MOUSE
TUMOURS
19
1.6.1.
LOH/AI
STUDIES
IN
HUMAN
TUMOURS
AND
THEIR
DISADVANTAGES
19
1.6.2.
ADVANTAGES
OF
MOUSE
MODELS
FOR
LOH/AI
STUDIES
20
1.6.3.
MOUSE
EXPERIMENTAL
SYSTEMS
FOR
LOH/AI
STUDIES
IN
TUMORIGENESIS
21
1.6.4.
A
MOUSE
MODEL
OF
RADIOGENIC
OSTEOSARCOMA
23
1.7.
AIM
OF
THIS
WORK
25
2.
MATERIALS
26
3.
METHODS
32
3.1.
OSTEOSARCOMA
INDUCTION
AND
COLLECTION
OF
TUMOUR
SAMPLES
32
3.2.
ISOLATION
OF
NUCLEIC
ACIDS
34
3.2.1.
ISOLATION
OF
TOTAL
RNA
AND
GENOMIC
DNA
FROM
FROZEN
TISSUE
34
3.2.2.
ISOLATION
OF
GENOMIC
DNA
FROM
FORMALIN
FIXED
TISSUE
35
3.2.3.
ISOLATION
OF
GENOMIC
DNA
FROM
MICRODISSECTED
FFPE
TISSUES
36
3.3.
QUANTIFICATION
OF
NUCLEIC
ACIDS
37
3.4.
VISUALISATION
OF
NUCLEIC
ACIDS
ON
AGAROSE
GEL
38
3.5.
GENERAL
MOLECULAR
BIOLOGY
METHODS
38
3.5.1.
REVERSE
TRANSCRIPTION
38
3.5.2.
PCR
AMPLIFICATION
39
3.5.3.
REAL-TIME
TAQMAN
PCR
40
3.5.4.
ELECTROPHORESIS
OF
THE
DNA/RNA
EXTRACTION
PRODUCTS
AND
PCR
AMPLIFICATION
PRODUCTS
43
3.5.5.
PURIFICATION
OF
THE
PCR
PRODUCT
44
3.5.6.
AUTOMATED
FLUORESCENT
SEQUENCING
45
3.6.
AMPLIFICATION
OF
DNA
MICROSATELLITES
47
3.6.1.
MOUSE
GENOME
DATABASES
USED
IN
THIS
WORK
47
3.6.2.
PRIMER
SELECTION
FOR
DNA
MICROSATELLITE
PCR
47
3.6.3.
PCR
AMPLIFICATION
OF
MICROSATELLITES
47
3.6.4.
CHOICE
OF
THE
METHOD
FOR
RESOLUTION
OF
THE
ALLELES
48
3.6.5.
TWO
COHORTS
OF
OSTEOSARCOMA
ANALYSED
49
3.6.6.
DOCUMENTATION
OF
MICROSATELLITE
GEL
IMAGES
49
3.7.
AMPLIFICATION
OF
THE
GENOMIC
DNA
FOR
SINGLE
NUCLEOTIDE
POLYMORPHISMS
50
3.7.1.
SELECTION
OF
GENOMIC
PRIMERS
50
3.7.2.
PCR
AMPLIFICATION
FROM
GENOMIC
DNA
50
3.7.3.
CONFIRMATION
OF
GENOMIC
DNA
SEQUENCES
51
3.8.
QUANTIFICATION
OF
THE
ALLELIC
RATIO
52
3.8.1.
QUANTIFICATION
OF
THE
ALLELIC
RATIO
USING
DIGITAL
IMAGES
52
3.8.2.
QUANTIFICATION
OF
THE
CHANGES
IN
ALLELIC
RATIO
AT
SNPS
LOCI
53
3.9.
AMPLIFICATION
OF
CDNA
FOR
MUTATION
ANALYSIS
53
3.9.1.
PCR
PRIMERS
FOR
CDNA
53
3.9.2.
PCR
AMPLIFICATION
OF
CDNA
55
3.9.3.
CONFIRMATION
OF
CDNA
SEQUENCES
56
3.10.
SOFTWARE
57
3.11.
STATISTICAL
ANALYSIS
METHODS
57
II
4.
RESULTS
58
4.1.
OSTEOSARCOMA
ARISE
IN
(BALB/C
X
CBA)
F1
HYBRIDS
WITH
A
SENSITIVITY
INTERMEDIATE
TO
THE
PARENTAL
STRAINS
58
4.2.
MICROSATELLITE-BASED
ALLELOTYPING
OF
SOMATIC
GENETIC
CHANGES
IN
MURINE
OSTEOSARCOMA
59
4.2.1.
SELECTION
OF
ALLELOTYPING
MARKERS
59
4.2.2.
VALIDATION
OF
THE
ALLELOTYPING
ASSAY
FOR
DETECTION
OF
LOH/AI
61
4.3.
NO
EVIDENCE
FOR
CONSISTENT
LOH/AI
ON
CHROMOSOMES
1,
2,
3,
5,
6,16,17,
AND
X
65
4.4.
EVIDENCE
FOR
NON-RANDOM
LOH/AI
ON
CHROMOSOMES
7,
8,10,12,13,15,
AND
18
70
4.4.1.
LOH/AI
ON
CHROMOSOME
7
70
4.4.2.
LOH/AI
ON
CHROMOSOME
8
72
4.4.3.
LOH/AI
ON
CHROMOSOME
10
74
4.4.4.
LOH/AI
ON
CHROMOSOME
12
76
4.4.5.
LOH/AI
ON
CHROMOSOME
13
78
4.4.6.
LOH/AI
ON
CHROMOSOME
15
80
4.4.7.
LOH/AI
ON
CHROMOSOME
18
82
4.5.
MAPPING
OF
THE
CANDIDATE
GENES
WITHIN
THE
MDR
ON
CHROMOSOMES
4,
9,11,14,
AND
19
86
4.5.1.
LOH/AI
ON
CHROMOSOME
4
86
4.5.2.
LOH/AI
ON
CHROMOSOME
9
93
4.5.3.
LOH/AI
ON
CHROMOSOME
11
96
4.5.4.
LOH/AI
ON
CHROMOSOME
14
109
4.5.5.
LOH/AI
ON
CHROMOSOME
19
114
4.6.
SUMMARY
OF
LOH/AI
DATA
120
4.6.1.
GENOME
WIDE
SOMATIC
ALTERATIONS
IN
A-RADIATION-INDUCED
MURINE
OSTEOSARCOMAS
AND
POSSIBLE
CO-OPERATION
MECHANISMS
120
4.6.2.
PARENTAL
ORIGIN
OF
ALLELES
INVOLVED
IN
ALLELIC
IMBALANCE
IN
MURINE
RADIOGENIC
OSTEOSARCOMA
123
4.6.3.
CHROMOSOMAL
INSTABILITY
IN
MOUSE
RADIOGENIC
OSTEOSARCOMAS
124
4.6.4.
COMPARISON
OF
THE
LOH/AI
OF
A
HIGH
MOLECULAR
WEIGHT
(H)
ALLELE
AND
THE
LOH/AI
OF
A
LOW
MOLECULAR
WEIGHT
(L)
ALLELE
126
III
5.
DISCUSSION
128
5.1.
MAPPING
OF
THE
REGIONS
OF
LAOSS
TO
THE
HUMAN
GENOME
128
5.2.
CANDIDATE
GENES
AFFECTED
BY
ALLELIC
IMBALANCE
IN
MOUSE
RADIOGENIC
OSTEOSARCOMA
132
5.2.1.
THE
KEY
ROLE
OF
TUMOUR
SUPPRESSORS,
P16
AND
RB1,
IN
MOUSE
RADIOGENIC
OSTEOSARCOMA
PATHOGENESIS
132
5.2.2.
LAOS-9.1,
LAOS-9.2,
AND
LAOS-11(P53)
SHOW
EVIDENCE
OF
SUPPLEMENTARY
CO-OPERATION
135
5.2.3.
LAOS-19
MAY
BE
ASSOCIATED
WITH
LOSS
OF
THE
TUMOUR
SUPPRESSOR
PTEN
137
5.2.4.
LAOSS
IMPLICATES
POSSIBLE
INVOLVEMENT
OF
CADHERINS
IN
THE
ETIOLOGY
OF
OSTEOSARCOMA
138
5.2.5.
LAOS-15.2
MAY
BE
ASSOCIATED
WITH
C-MYC
AMPLIFICATION
139
5.2.6.
OTHER
LAOSS
AFFECTED
IN
MOUSE
RADIOGENIC
OSTEOSARCOMA
140
5.3.
MARKERS
OF
MURINE
OSTEOBLASTIC
OSTEOSARCOMA
DEVELOPMENT
AND
PROGRESSION
142
5.4.
CHROMOSOMAL
INSTABILITY
IN
MOUSE
AND
HUMAN
OSTEOSARCOMA
144
6.
CONCLUSIONS
147
7.
REFERENCES
149
8.
APPENDIX
164
IV |
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author | Kuosaite, Virginija 1963- |
author_GND | (DE-588)123559820 |
author_facet | Kuosaite, Virginija 1963- |
author_role | aut |
author_sort | Kuosaite, Virginija 1963- |
author_variant | v k vk |
building | Verbundindex |
bvnumber | BV014141973 |
ctrlnum | (OCoLC)163259804 (DE-599)BVBBV014141973 |
format | Thesis Book |
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genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
genre_facet | Hochschulschrift |
id | DE-604.BV014141973 |
illustrated | Illustrated |
indexdate | 2024-08-17T00:43:13Z |
institution | BVB |
language | English |
oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009690411 |
oclc_num | 163259804 |
open_access_boolean | |
owner | DE-19 DE-BY-UBM DE-12 DE-355 DE-BY-UBR DE-188 |
owner_facet | DE-19 DE-BY-UBM DE-12 DE-355 DE-BY-UBR DE-188 |
physical | IV, 189 S. Ill., graph. Darst. |
publishDate | 2001 |
publishDateSearch | 2001 |
publishDateSort | 2001 |
record_format | marc |
spelling | Kuosaite, Virginija 1963- Verfasser (DE-588)123559820 aut Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma Virginija Kuosaite 2001 IV, 189 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Univ., Diss., 2001 Maus (DE-588)4169148-9 gnd rswk-swf Allel (DE-588)4271150-2 gnd rswk-swf Osteosarkom (DE-588)4172929-8 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Maus (DE-588)4169148-9 s Osteosarkom (DE-588)4172929-8 s Allel (DE-588)4271150-2 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009690411&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Kuosaite, Virginija 1963- Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma Maus (DE-588)4169148-9 gnd Allel (DE-588)4271150-2 gnd Osteosarkom (DE-588)4172929-8 gnd |
subject_GND | (DE-588)4169148-9 (DE-588)4271150-2 (DE-588)4172929-8 (DE-588)4113937-9 |
title | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma |
title_auth | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma |
title_exact_search | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma |
title_full | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma Virginija Kuosaite |
title_fullStr | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma Virginija Kuosaite |
title_full_unstemmed | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma Virginija Kuosaite |
title_short | Mapping of allelic imbalance in alpha-particle-radiation-induced murine osteosarcoma |
title_sort | mapping of allelic imbalance in alpha particle radiation induced murine osteosarcoma |
topic | Maus (DE-588)4169148-9 gnd Allel (DE-588)4271150-2 gnd Osteosarkom (DE-588)4172929-8 gnd |
topic_facet | Maus Allel Osteosarkom Hochschulschrift |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009690411&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
work_keys_str_mv | AT kuosaitevirginija mappingofallelicimbalanceinalphaparticleradiationinducedmurineosteosarcoma |