Identification of specific gene copy number changes in asbestos-related lung cancer

Our plain-English summary of Identification of specific gene copy number changes in asbestos-related lung cancer, by P. Nymark, H. Wikman, S. Ruosaari, et al (Cancer Research, 2006).

The study

• Authors: P. Nymark, H. Wikman, S. Ruosaari, J. Hollmén, E. Vanhala, A. Karjalainen, S. Anttila, S. Knuutila
• Journal: Cancer Research
• Published: 2006;66(11):5737-43
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos is a well-known lung cancer-causing mineral fiber. In vitro and in vivo experiments have shown that asbestos can cause chromosomal damage and aberrations. Lung tumors, in general, have several recurrently amplified and deleted chromosomal regions. To investigate whether a distinct chromosomal aberration profile could be detected in the lung tumors of heavily asbestos-exposed patients, we analyzed the copy number profiles of 14 lung tumors from highly asbestos-exposed patients and 14 matched tumors from nonexposed patients using classic comparative genomic hybridization (CGH). A specific profile could lead to identification of the underlying genes that may act as mediators of tumor formation and progression. In addition, array CGH analyses on cDNA microarrays (13,000 clones) were carried out on 20 of the same patients. Classic CGH showed, on average, more aberrations in asbestos-exposed than in nonexposed patients, and an altered region in chromosome 2 seemed to occur more frequently in the asbestos-exposed patients. Array CGH revealed aberrations in 18 regions that were significantly associated with either of the two groups. The most significant regions were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2, and 19p13.1-p13.3 (P < 0.005). Furthermore, 11 fragile sites coincided with the 18 asbestos-associated regions (P = 0.08), which may imply preferentially caused DNA damage at these sites. Our findings are the first evidence, indicating that asbestos exposure may produce a specific DNA damage profile.

In plain English

This laboratory study, by researchers in Helsinki, Finland, compared genetic changes in lung tumors removed during lung cancer surgery. It used tumors from 14 highly asbestos-exposed patients and 14 nonexposed patients matched for age, gender, nationality and smoking history. Exposed patients had definite or probable exposure at work and more than 5 million asbestos fibers per gram of dry lung tissue. The article does not name fiber types. The authors used classic comparative genomic hybridization (CGH), a method that detects gained or lost stretches of chromosomes, on all 28 tumors, and array CGH on 20. In tumor types other than squamous cell carcinoma, exposed patients averaged 6.4 changes and nonexposed patients 2.8. A gain at chromosome region 2p23 occurred in 8 of 14 exposed and 2 of 14 nonexposed patients (P = 0.025). Array CGH found 18 regions whose copy number differed between the groups. Eleven known fragile sites fell within these regions (P = 0.08). The authors concluded that asbestos exposure may produce a specific DNA damage profile. They said a larger series of patients is needed to verify this.

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 tumor tissue comparing asbestos-exposed and matched nonexposed lung cancer patients, using classic comparative genomic hybridization (CGH) on all tumors and array CGH on a subset
• Who was studied: Lung tumors from 14 highly asbestos-exposed patients and 14 nonexposed patients matched for age, gender, nationality and smoking history, obtained during lung cancer surgery (Finnish Institute of Occupational Health and University of Helsinki). Array CGH was done on 20 samples: 11 exposed and 9 nonexposed.
• Exposure: Asbestos exposure estimated from work history taken by personal interview, plus an electron microscopic count of asbestos fibers in lung tissue. The exposed group had definite or probable exposure by work history and more than 5 million fibers per gram dry weight. Fiber types are not specified.
• Main results:
  • Classic CGH: in all histologic types except squamous cell carcinoma, the exposed group had slightly more chromosomal aberrations (mean 6.4 in exposed vs 2.8 in nonexposed)
  • Among squamous cell carcinomas, tumors of nonexposed patients showed more aberrations than those of exposed patients
  • Classic CGH: an amplification at 2p23 was present in 57% (8 of 14) of exposed patients and 14% (2 of 14) of nonexposed patients (P = 0.025)
  • Array CGH: 18 regions differed significantly in DNA copy number between the exposed and nonexposed groups
  • The most significant regions (P < 0.005) were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 and 19p13.1-p13.3
  • None of the 18 regions showed a high copy number change; each was a low-level gain or a low-level deletion
  • The gain at 2p appeared specific to the exposed group in both array CGH and classic CGH
  • Eleven of the 125 known fragile sites coincided with the 18 regions (P = 0.08)
• The authors' conclusion: The authors concluded that their findings are the first evidence indicating that asbestos exposure may produce a specific DNA damage profile in lung tumors. They called for a larger series of patients to verify this.
• Limitations the authors state:
  • The combined array analysis may not fully compensate for noise caused by contamination with normal cells, so a gain in one group could be misread as a loss in the other
  • Classic CGH found more gains than losses, probably because the tumor material was not microdissected
  • Classic CGH failed to detect two large regions of loss, probably because of normal cell contamination
  • A larger series of patients is needed to verify the findings

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mineral Fiber, Asbestos Exposure.

Related studies

• Gene expression profiling and gene copy-number changes in malignant mesothelioma cell lines — C. Zanazzi, R. Hersmus, et al. (2007)
• DNA copy number changes in familial malignant mesothelioma — V. Ascoli, Y. Aalto, et al. (2001)
• Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer — H. Wikman, S. Ruosaari, et al. (2007)
• DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure — E. Kettunen, M. Aavikko, et al. (2009)
• Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer — E. Kettunen, K. Salmenkivi, et al. (2006)
• 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)

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