Limits...
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.

Show MeSH

Related in: MedlinePlus

Multiple centrosomes (γ-tubulin, red) in mononucleated (A), binucleated (B), and pentanucleated cells (C) in cases 1, 2, and 8, respectively. Normal (D) and multipolar (E and F) mitotic figures in cases 5, 8, and 4, respectively; the β-tubulin fluor layer (green) has been removed for clarity in (F). Non-clonal telomeric associations between two chromosomes 15 and one chromosome 22 (G) and an unbalanced 4;15-translocation (H) in addition to the clonal 8;8-translocation (G and H, top row) demonstrated by multicolour karyotyping in case 1. Another cell from the same case shows absence of TTAGGG signals at the q termini of two chromosomes 15, one of which is involved in a telomeric association (I). In other cells, absence of TTAGGG signals was observed at several termini (J), including 15p and q (asterisks).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2376110&req=5

fig3: Multiple centrosomes (γ-tubulin, red) in mononucleated (A), binucleated (B), and pentanucleated cells (C) in cases 1, 2, and 8, respectively. Normal (D) and multipolar (E and F) mitotic figures in cases 5, 8, and 4, respectively; the β-tubulin fluor layer (green) has been removed for clarity in (F). Non-clonal telomeric associations between two chromosomes 15 and one chromosome 22 (G) and an unbalanced 4;15-translocation (H) in addition to the clonal 8;8-translocation (G and H, top row) demonstrated by multicolour karyotyping in case 1. Another cell from the same case shows absence of TTAGGG signals at the q termini of two chromosomes 15, one of which is involved in a telomeric association (I). In other cells, absence of TTAGGG signals was observed at several termini (J), including 15p and q (asterisks).

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


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)

Multiple centrosomes (γ-tubulin, red) in mononucleated (A), binucleated (B), and pentanucleated cells (C) in cases 1, 2, and 8, respectively. Normal (D) and multipolar (E and F) mitotic figures in cases 5, 8, and 4, respectively; the β-tubulin fluor layer (green) has been removed for clarity in (F). Non-clonal telomeric associations between two chromosomes 15 and one chromosome 22 (G) and an unbalanced 4;15-translocation (H) in addition to the clonal 8;8-translocation (G and H, top row) demonstrated by multicolour karyotyping in case 1. Another cell from the same case shows absence of TTAGGG signals at the q termini of two chromosomes 15, one of which is involved in a telomeric association (I). In other cells, absence of TTAGGG signals was observed at several termini (J), including 15p and q (asterisks).
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Multiple centrosomes (γ-tubulin, red) in mononucleated (A), binucleated (B), and pentanucleated cells (C) in cases 1, 2, and 8, respectively. Normal (D) and multipolar (E and F) mitotic figures in cases 5, 8, and 4, respectively; the β-tubulin fluor layer (green) has been removed for clarity in (F). Non-clonal telomeric associations between two chromosomes 15 and one chromosome 22 (G) and an unbalanced 4;15-translocation (H) in addition to the clonal 8;8-translocation (G and H, top row) demonstrated by multicolour karyotyping in case 1. Another cell from the same case shows absence of TTAGGG signals at the q termini of two chromosomes 15, one of which is involved in a telomeric association (I). In other cells, absence of TTAGGG signals was observed at several termini (J), including 15p and q (asterisks).
Mentions: Positive correlation r=0.96 (Pearson; P<0.05) between the frequency of multipolar mitoses and anaphase bridges.

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