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Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres.
- Source :
-
British journal of cancer [Br J Cancer] 2002 Jul 15; Vol. 87 (2), pp. 202-7. - Publication Year :
- 2002
-
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, 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.
- Subjects :
- Adenoma, Pleomorphic enzymology
Adenoma, Pleomorphic genetics
Carcinoma, Squamous Cell enzymology
Carcinoma, Squamous Cell genetics
DNA-Binding Proteins
Female
Head and Neck Neoplasms enzymology
Head and Neck Neoplasms genetics
Humans
Karyotyping
Male
Mitosis
Neoplasm Proteins analysis
Parotid Neoplasms enzymology
Parotid Neoplasms genetics
Repetitive Sequences, Nucleic Acid
Telomerase analysis
Adenoma, Pleomorphic ultrastructure
Carcinoma, Squamous Cell ultrastructure
Centrosome ultrastructure
Chromosome Aberrations
DNA, Neoplasm analysis
Head and Neck Neoplasms ultrastructure
Parotid Neoplasms ultrastructure
Telomere chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 87
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 12107843
- Full Text :
- https://doi.org/10.1038/sj.bjc.6600438