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

Gisselsson D, Jonson T, Yu C, Martins C, Mandahl N, Wiegant J, Jin Y, Mertens F, Jin C - Br. J. Cancer (2002)

Bottom Line: 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.In turn, this may cause an accumulation of centrosomes and mitotic multipolarity.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. david.gisselsson@klingen.lu.se

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.

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Related in: MedlinePlus

Positive correlation r=0.96 (Pearson; P<0.05) between the frequency of multipolar mitoses and anaphase bridges.
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fig2: Positive correlation r=0.96 (Pearson; P<0.05) between the frequency of multipolar mitoses and anaphase bridges.

Mentions: Broken (A) and intact (B and C) anaphase bridges in cases 2, 5 and 8, respectively, and multipolar metaphase (D and E) and anaphase (F) cells in case 8; haematoxylin-eosin staining.


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

Gisselsson D, Jonson T, Yu C, Martins C, Mandahl N, Wiegant J, Jin Y, Mertens F, Jin C - Br. J. Cancer (2002)

Positive correlation r=0.96 (Pearson; P<0.05) between the frequency of multipolar mitoses and anaphase bridges.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376110&req=5

fig2: Positive correlation r=0.96 (Pearson; P<0.05) between the frequency of multipolar mitoses and anaphase bridges.
Mentions: Broken (A) and intact (B and C) anaphase bridges in cases 2, 5 and 8, respectively, and multipolar metaphase (D and E) and anaphase (F) cells in case 8; haematoxylin-eosin staining.

Bottom Line: 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.In turn, this may cause an accumulation of centrosomes and mitotic multipolarity.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. david.gisselsson@klingen.lu.se

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.

Show MeSH
Related in: MedlinePlus