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Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres.

Gisselsson, D LU ; Jonson, T LU ; Yu, C; Martins, C; Mandahl, N LU ; Wiegant, J; Jin, Y LU ; Mertens, F LU and Jin, C LU (2002) In British Journal of Cancer 87(2). p.202-207
Abstract

Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant,... (More)

Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution.

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keywords
Adenoma, Pleomorphic, Carcinoma, Squamous Cell, Centrosome, Chromosome Aberrations, DNA, Neoplasm, DNA-Binding Proteins, Female, Head and Neck Neoplasms, Humans, Karyotyping, Male, Mitosis, Neoplasm Proteins, Parotid Neoplasms, Repetitive Sequences, Nucleic Acid, Telomerase, Telomere, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
British Journal of Cancer
volume
87
issue
2
pages
6 pages
publisher
Nature Publishing Group
external identifiers
  • wos:000177142300013
  • pmid:12107843
  • scopus:0017897331
ISSN
1532-1827
DOI
10.1038/sj.bjc.6600438
language
English
LU publication?
yes
id
004b9586-2e25-4c25-baae-8dc241bb0d30 (old id 109195)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12107843&dopt=Abstract
date added to LUP
2007-07-06 14:17:55
date last changed
2017-01-03 08:43:27
@article{004b9586-2e25-4c25-baae-8dc241bb0d30,
  abstract     = {<p>Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution.</p>},
  author       = {Gisselsson, D and Jonson, T and Yu, C and Martins, C and Mandahl, N and Wiegant, J and Jin, Y and Mertens, F and Jin, C},
  issn         = {1532-1827},
  keyword      = {Adenoma, Pleomorphic,Carcinoma, Squamous Cell,Centrosome,Chromosome Aberrations,DNA, Neoplasm,DNA-Binding Proteins,Female,Head and Neck Neoplasms,Humans,Karyotyping,Male,Mitosis,Neoplasm Proteins,Parotid Neoplasms,Repetitive Sequences, Nucleic Acid,Telomerase,Telomere,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {07},
  number       = {2},
  pages        = {202--207},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres.},
  url          = {http://dx.doi.org/10.1038/sj.bjc.6600438},
  volume       = {87},
  year         = {2002},
}