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Mechanisms and Consequences of Chromosomal Instability in Malignant tumours

Stewénius, Ylva LU (2008) In Lund University Faculty of Medicine Doctoral Dissertation Series 2008:10.
Abstract
In this thesis, telomere deficiency with subsequent anaphase bridging was found to be associated with chromosomal instability in established colorectal cancer cell lines and in Wilms tumour. In colorectal cancer cell lines, anaphase bridging was observed to generate both numerical and structural chromosomal aberrations and was also associated with the presence of multipolar mitoses. In contrast to cells having undergone anaphase bridging, daughter cells from these multipolar mitotic figures were observed not to form clones in culture, possibly because of the severe aneuploidy which is the result of multipolar mitosis. Chromosomal instability was observed also in colorectal cancer cell lines with mutations in the mismatch repair genes. In... (More)
In this thesis, telomere deficiency with subsequent anaphase bridging was found to be associated with chromosomal instability in established colorectal cancer cell lines and in Wilms tumour. In colorectal cancer cell lines, anaphase bridging was observed to generate both numerical and structural chromosomal aberrations and was also associated with the presence of multipolar mitoses. In contrast to cells having undergone anaphase bridging, daughter cells from these multipolar mitotic figures were observed not to form clones in culture, possibly because of the severe aneuploidy which is the result of multipolar mitosis. Chromosomal instability was observed also in colorectal cancer cell lines with mutations in the mismatch repair genes. In Wilms tumour, chromosomal instability was found to be associated with an aggressive tumour phenotype and poor survival. Telomere shortening was more pronounced in the immature tumour components, which could explain the fact that anaphase bridges and multipolar mitoses were only observed in these tumour elements. Because of breakage-fusion-bridge cycles, chromosomal instability is associated with karyotypes with extensive structural chromosomal rearrangements. By applying a combination of subtelomeric FISH, G-banding and multicolour FISH, a high resolution for cytogenetic analysis of tumours with chromosomal instability could be obtained. This combined approached was used also to search for reciprocal translocations leading to fusion genes in Wilms tumour. Although the technique proved efficient, no recurrent reciprocal translocation was found in Wilms tumour. Our results indicate that telomere dependent chromosomal instability is present in both colorectal cancer and Wilms tumour and could be an important prognostic factor in Wilms tumours. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Pritchard-Jones, Kathy, Royal Marsden Hospital and Institute of Cancer Research, Surrey, UK.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
structural rearrangement, Ewing family tumour, Chromosomal instability, nephroblastoma, Wilms tumour, chromosomal aberration, anaphase bridge, subtelomeric FISH, breakage-fusion-bridge cycle
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2008:10
pages
88 pages
publisher
Divison of Clinical Genetics
defense location
Segerfalksalen, BMC
defense date
2008-02-29 10:00
ISSN
1652-8220
ISBN
978-91-85897-63-6
language
English
LU publication?
yes
id
aa25f70d-eeff-4b07-b685-79500a554219 (old id 1022212)
date added to LUP
2008-02-04 11:21:41
date last changed
2016-09-19 08:44:46
@phdthesis{aa25f70d-eeff-4b07-b685-79500a554219,
  abstract     = {In this thesis, telomere deficiency with subsequent anaphase bridging was found to be associated with chromosomal instability in established colorectal cancer cell lines and in Wilms tumour. In colorectal cancer cell lines, anaphase bridging was observed to generate both numerical and structural chromosomal aberrations and was also associated with the presence of multipolar mitoses. In contrast to cells having undergone anaphase bridging, daughter cells from these multipolar mitotic figures were observed not to form clones in culture, possibly because of the severe aneuploidy which is the result of multipolar mitosis. Chromosomal instability was observed also in colorectal cancer cell lines with mutations in the mismatch repair genes. In Wilms tumour, chromosomal instability was found to be associated with an aggressive tumour phenotype and poor survival. Telomere shortening was more pronounced in the immature tumour components, which could explain the fact that anaphase bridges and multipolar mitoses were only observed in these tumour elements. Because of breakage-fusion-bridge cycles, chromosomal instability is associated with karyotypes with extensive structural chromosomal rearrangements. By applying a combination of subtelomeric FISH, G-banding and multicolour FISH, a high resolution for cytogenetic analysis of tumours with chromosomal instability could be obtained. This combined approached was used also to search for reciprocal translocations leading to fusion genes in Wilms tumour. Although the technique proved efficient, no recurrent reciprocal translocation was found in Wilms tumour. Our results indicate that telomere dependent chromosomal instability is present in both colorectal cancer and Wilms tumour and could be an important prognostic factor in Wilms tumours.},
  author       = {Stewénius, Ylva},
  isbn         = {978-91-85897-63-6},
  issn         = {1652-8220},
  keyword      = {structural rearrangement,Ewing family tumour,Chromosomal instability,nephroblastoma,Wilms tumour,chromosomal aberration,anaphase bridge,subtelomeric FISH,breakage-fusion-bridge cycle},
  language     = {eng},
  pages        = {88},
  publisher    = {Divison of Clinical Genetics},
  school       = {Lund University},
  series       = {Lund University Faculty of Medicine Doctoral Dissertation Series},
  title        = {Mechanisms and Consequences of Chromosomal Instability in Malignant tumours},
  volume       = {2008:10},
  year         = {2008},
}