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Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes
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  • Published: 09 April 1999

Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes

  • P M De Angelis1,
  • O P F Clausen1,
  • A Schjølberg1 &
  • …
  • T Stokke2 

British Journal of Cancer volume 80, pages 526–535 (1999)Cite this article

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Summary

Comparative genomic hybridization (CGH) is used to detect amplified and/or deleted chromosomal regions in tumours by mapping their locations on normal metaphase chromosomes. Forty-five sporadic colorectal carcinomas were screened for chromosomal aberrations using direct CGH. The median number of chromosomal aberrations per tumour was 7.0 (range 0–19). Gains of 20q (67%) and losses of 18q (49%) were the most frequent aberrations. Other recurrent gains of 5p, 6p, 7, 8q, 13q, 17q, 19, X and losses of 1p, 3p, 4, 5q, 6q, 8p, 9p, 10, 15q, 17p were found in > 10% of colorectal tumours. High-level gains (ratio > 1.5) were seen only on 8q, 13q, 20 and X, and only in DNA aneuploid tumours. DNA aneuploid tumours had significantly more chromosomal aberrations (median number per tumour of 9.0) compared to diploid tumours (median of 1.0) (P < 0.0001). The median numbers of aberrations seen in DNA hyperdiploid and highly aneuploid tumours were not significantly different (8.5 and 11.0 respectively; P = 0.58). Four tumours had no detectable chromosomal aberrations and these were DNA diploid. A higher percentage of tumours from male patients showed Xq gain and 18q loss compared to tumours from female patients (P = 0.05 and 0.01 respectively). High tumour S phase fractions were associated with gain of 20q13 (P = 0.03), and low tumour apoptotic indices were associated with loss of 4q (P = 0.05). Tumours with TP53 mutations had more aberrations (median of 9.0 per tumour) compared to those without (median of 2.0) (P = 0.002), and gain of 8q23–24 and loss of 18qcen-21 were significantly associated with TP53 mutations (P = 0.04 and 0.02 respectively). Dukes’ C/D stage tumours tended to have a higher number of aberrations per tumour (median of 10.0) compared to Dukes’ B tumours (median of 3.0) (P = 0.06). The low number of aberrations observed in DNA diploid tumours compared to aneuploid tumours suggests that genomic instability and possible growth advantages in diploid tumours do not result from acquisition of gross chromosomal aberrations but rather from selection for other types of mutations. Our study is consistent with the idea that these two groups of tumours evolve along separate genetic pathways and that gross genomic instability is associated with TP53 gene aberrations.

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  1. Institute of Pathology, The Norwegian National Hospital, Oslo, 0027, Norway

    P M De Angelis, O P F Clausen & A Schjølberg

  2. Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    T Stokke

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Angelis, P., Clausen, O., Schjølberg, A. et al. Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer 80, 526–535 (1999). https://doi.org/10.1038/sj.bjc.6690388

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  • Received: 22 July 1998

  • Revised: 23 October 1998

  • Accepted: 04 November 1998

  • Published: 09 April 1999

  • Issue date: 01 May 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690388

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Keywords

  • colorectal tumours
  • direct CGH
  • gains
  • losses
  • oncogenes
  • tumour suppressor genes

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