Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma

Our plain-English summary of Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma, by A.M. Björkqvist, L. Tammilehto, S. Anttila, et al (British Journal of Cancer, 1997).

The study

• Authors: A.M. Björkqvist, L. Tammilehto, S. Anttila, K. Mattson, S. Knuutila
• Journal: British Journal of Cancer
• Published: 1997;75(4):523-7
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Comparative genomic hybridization (CGH) analyses were performed on 27 human pleural mesothelioma tumour specimens, consisting of 18 frozen tumours and nine paraffin-embedded tumours, to screen for gains and losses of DNA sequences. Copy number changes were detected in 15 of the 27 specimens with a range from one to eight per specimen. On average, more losses than gains of genetic material were observed. The loss of DNA sequences occurred most commonly in the short arm of chromosome 9 (p21-pter), in 60% of the abnormal specimens. Other losses among the abnormal specimens were frequently detected in the long arms of chromosomes 4 (q31.1-qter, 20%), 6 (q22-q24, 33%), 13 (33%),14 (q24-qter, 33%) and 22 (q13, 20%). A gain in DNA sequences was found in the long arm of chromosome 1 (cen-qter) in 33% of the abnormal specimens. Our analysis is the first genome-wide screening for gains and losses of DNA sequences using comparative genomic hybridization in malignant pleural mesothelioma tumours. The recurrent DNA sequence changes detected in this study suggest that the corresponding chromosomal areas most probably contain genes important for the initiation and progression of mesothelioma.

In plain English

This laboratory study from Finland used a technique called comparative genomic hybridization to look for places in the chromosomes where tumour DNA had been lost or gained. The authors tested 27 tumour specimens from patients with malignant pleural mesothelioma (23 men and 4 women). Seventeen patients had a known history of asbestos exposure; the article does not name fiber types. Changes were found in 15 of the 27 specimens: 6 of 8 epithelial and 9 of 18 mixed specimens, and none in the single sarcomatous specimen. Losses (40) outnumbered gains (12). The most common change was loss of part of the short arm of chromosome 9, in 9 of the 15 abnormal specimens (60%). Losses on chromosomes 4, 6, 13, 14 and 22 and a gain on chromosome 1 also recurred. Some pairs of changes were statistically significantly linked to each other. No change was statistically linked to survival or to asbestos exposure. The authors concluded these regions may contain genes involved in the tumour's development and progression. They noted that normal cells within samples may have hidden some changes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory genetic study of tumour specimens using comparative genomic hybridization (CGH) to screen all chromosomes for gains and losses of DNA
• Who was studied: 27 tumour specimens from patients with malignant pleural mesothelioma from the catchment area of Helsinki University Central Hospital, Finland. There were 8 epithelial, 18 mixed and 1 sarcomatous specimens. Patients were 4 women and 23 men, median age 59 years (range 39 to 74). Specimens were 18 frozen and 9 paraffin-embedded tumours. Collection dates are not given.
• Exposure: Seventeen of the 27 patients had a known history of asbestos exposure. No fiber types, products, jobs or doses are reported. The study's focus was DNA changes in the tumours, not exposure.
• Main results:
  • DNA copy number changes were found in 15 of the 27 specimens, with one to eight changes per abnormal specimen.
  • By tumour type, changes were found in 75% (6/8) of epithelial specimens and 50% (9/18) of mixed specimens. None were found in the one sarcomatous specimen.
  • Losses of DNA outnumbered gains by a ratio of 3.3 to 1 (40 losses and 12 gains).
  • The most frequent change was loss in the short arm of chromosome 9 (smallest common region 9p21 to the end of the arm), in 9 of the 15 abnormal tumours (60%).
  • Other regions commonly lost among the 15 abnormal tumours: 4q31.1-qter (three cases, 20%), 6q22-q24 (five cases, 33%), 13q (five cases, 33%), 14q24-qter (five cases, 33%) and 22q13 (three cases, 20%).
  • The most common gain was in the long arm of chromosome 1, in five of the 15 abnormal cases (33%).
  • No highly amplified chromosome regions were found.
  • Loss on 6q appeared more likely in epithelial tumours than in mixed and sarcomatous tumours combined, but this was not statistically significant (odds ratio 5.1, 90% confidence interval 0.9 to 20.5, P = 0.28).
  • There were statistically significant correlations for simultaneous loss of 9p together with either 6q or 13q, and for simultaneous gain of 1q with loss of 14q. The article prints a single figure (odds ratio 13.6, 95% confidence interval 1.2 to 151, P = 0.03) immediately after the 1q gain and 14q loss pairing.
  • None of the DNA changes showed a statistical correlation with patients' survival or with their asbestos exposure.
• The authors' conclusion: The authors concluded that the DNA changes clustered on chromosomes 1q, 4q, 6q, 9p, 13q, 14q and 22q. They suggested these regions could hold currently unknown genes that may be involved in the development and progression of mesothelioma.
• Limitations the authors state:
  • The authors attributed the 12 normal results probably to contamination by normal cells or to genetic variation within the tumours.
  • Changes reported in earlier cytogenetic studies (gains of chromosomes 5, 7 and 20 and losses of 3p) were not seen. The authors suggested these may have been present in too few cells for the method to detect.
  • The number of cases was small, so Fisher's exact test was used.
  • Some chromosome regions (1p32-pter, 16p, 19 and 22) were interpreted with special caution because they are known to give false positive results.
  • Whether the p15 and p16 genes were lost in the nine specimens with 9p deletion was not determined.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma.

Related studies

• Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array — P. Chirac, D. Maillet, et al. (2016)
• DNA copy number changes in familial malignant mesothelioma — V. Ascoli, Y. Aalto, et al. (2001)
• Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung — A.M. Björkqvist, L. Tammilehto, et al. (1998)
• Identification of specific gene copy number changes in asbestos-related lung cancer — P. Nymark, H. Wikman, et al. (2006)
• The potential value of comparative genomic hybridization analysis in effusion-and fine needle aspiration cytology — H. Nagel, H.J. Schulten, et al. (2002)
• Familial pleural mesothelioma with environmental asbestos exposure: losses of DNA sequences by comparative genomic hybridization (CGH) — G. Serio, A. Scattone, et al. (2004)

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