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

TERT RNA expression measured by reverse transcriptase–PCR with primers outside the alternatively spliced region (TERT3′, left) and primers for four alternative splice products (TERT, right). TERT3′ expression as well as two major (239 and 421 bp) and two minor (275 and 457 bp) TERT products are present in thymus (T) and the HNSCC cases 4, 5, 7 and 8, but not in kidney (K), pancreas (P), or the other head and neck tumours; β-actin (ACTB) was used as internal control.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2376110&req=5

fig4: TERT RNA expression measured by reverse transcriptase–PCR with primers outside the alternatively spliced region (TERT3′, left) and primers for four alternative splice products (TERT, right). TERT3′ expression as well as two major (239 and 421 bp) and two minor (275 and 457 bp) TERT products are present in thymus (T) and the HNSCC cases 4, 5, 7 and 8, but not in kidney (K), pancreas (P), or the other head and neck tumours; β-actin (ACTB) was used as internal control.

Mentions: Human telomerase activity is determined by the expression of its reverse transcriptase subunit, TERT. However, the TERT transcript is alternatively spliced, and only the expression of full-length messages correlates with enzyme activity (Ulaner et al, 1998). Reverse transcriptase–PCR analysis revealed expression of full-length TERT in all HNC except in case 6, but in none of the PA (Figure 4Figure 4


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)

TERT RNA expression measured by reverse transcriptase–PCR with primers outside the alternatively spliced region (TERT3′, left) and primers for four alternative splice products (TERT, right). TERT3′ expression as well as two major (239 and 421 bp) and two minor (275 and 457 bp) TERT products are present in thymus (T) and the HNSCC cases 4, 5, 7 and 8, but not in kidney (K), pancreas (P), or the other head and neck tumours; β-actin (ACTB) was used as internal control.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: TERT RNA expression measured by reverse transcriptase–PCR with primers outside the alternatively spliced region (TERT3′, left) and primers for four alternative splice products (TERT, right). TERT3′ expression as well as two major (239 and 421 bp) and two minor (275 and 457 bp) TERT products are present in thymus (T) and the HNSCC cases 4, 5, 7 and 8, but not in kidney (K), pancreas (P), or the other head and neck tumours; β-actin (ACTB) was used as internal control.
Mentions: Human telomerase activity is determined by the expression of its reverse transcriptase subunit, TERT. However, the TERT transcript is alternatively spliced, and only the expression of full-length messages correlates with enzyme activity (Ulaner et al, 1998). Reverse transcriptase–PCR analysis revealed expression of full-length TERT in all HNC except in case 6, but in none of the PA (Figure 4Figure 4

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