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Abnormal nuclear shape in solid tumors reflects mitotic instability.

D Gisselsson1, J Björk, M Höglund

  • 1Departments of Clinical Genetics, Occupational and Environmental Medicine, and Pathology, University Hospital, Lund, Sweden. david.gisselsson@klingen.lu.se

The American Journal of Pathology
|January 6, 2001
PubMed
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Abnormal nuclear shape in tumors indicates genetic instability. Nuclear blebs, chromatin strings, and micronuclei are linked to unstable chromosomes and breakage-fusion-bridge events, serving as indicators of tumor heterogeneity.

Area of Science:

  • Cell Biology
  • Genetics
  • Oncology

Background:

  • Abnormal nuclear morphology is common in cancer but poorly understood.
  • Mechanisms linking nuclear shape changes to genetic instability require elucidation.

Purpose of the Study:

  • To investigate the relationship between abnormal nuclear shape and chromosomal instability in tumor cells.
  • To determine if nuclear abnormalities serve as indicators of genetic instability and intratumor heterogeneity.

Main Methods:

  • Fluorescence in situ hybridization (FISH) to identify unstable chromosomes (ring and dicentric) in metaphase and interphase nuclei.
  • Evaluation of nuclear morphology (blebs, chromatin strings, micronuclei) in short-term tumor cell cultures and irradiated cell lines.
  • Correlation analysis between nuclear abnormalities, unstable chromosomes, anaphase bridges, and karyotypic patterns.

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Main Results:

  • A high percentage (71-86%) of nuclear blebs, chromatin strings, and micronuclei contained material from unstable chromosomes.
  • Strong linear correlations were observed between nuclear shape abnormalities and the frequency of unstable chromosomes (r=0.87) and anaphase bridges (r=0.98).
  • Nuclear abnormalities were significantly more frequent in tumors with unstable chromosomal aberrations and positively correlated with intratumor heterogeneity (r=0.78).

Conclusions:

  • Nuclear blebs, chromatin strings, and micronuclei formation in malignant tissues are closely linked to breakage-fusion-bridge mitotic disturbances.
  • Abnormal nuclear shape serves as a key indicator of genetic instability and intratumor heterogeneity in cancer.
  • Nuclear morphology changes reflect underlying chromosomal instability, irrespective of tumor grade or cytogenetic complexity.