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

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Author

Summary, in English

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.

Publishing year

2002-07-15

Language

English

Pages

202-207

Publication/Series

British Journal of Cancer

Volume

87

Issue

2

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1532-1827