Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis

Our plain-English summary of Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis, by A.M. Björkqvist, M. Wolf, S. Nordling, et al (British Journal of Cancer, 1999).

The study

• Authors: A.M. Björkqvist, M. Wolf, S. Nordling, L. Tammilehto, A. Knuuttila, J. Kere, K. Mattson, S. Knuutila
• Journal: British Journal of Cancer
• Published: 1999;81(7):1111-5
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma.

In plain English

This laboratory study examined chromosome 14 in tumours from 18 malignant mesothelioma patients operated on at Helsinki University Central Hospital in 1995–1997 (15 men, 3 women; 13 with a clear history of asbestos exposure). The authors compared tumour DNA with each patient's blood DNA at 23 genetic markers along the long arm of chromosome 14 (14q). Ten of the 18 tumours (56%) showed a deletion at one or more markers. Only one tumour had a deletion at every informative marker; the rest had partial deletions. The regions 14q11.1–q12 and 14q23–q24 were most often affected. Deletions were found in 9 of 11 patients with stage 2 or 3 disease versus 1 of 7 with stage 4 (P = 0.013). They were found in 9 of 13 tumours from asbestos-exposed patients versus 1 of 5 without known exposure, a difference that was not statistically significant. Median survival was 12 months with deletions and 20 months without, also not statistically significant. The authors said the small sample does not allow decisive conclusions. They concluded that 14q losses are more frequent in mesothelioma than previously recognized by other methods.

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 tissue: microsatellite marker analysis (loss of heterozygosity and allelic imbalance) of chromosome 14q, compared with each patient's normal blood DNA
• Who was studied: 18 primary malignant mesothelioma tumours from patients who had surgery at Helsinki University Central Hospital, Finland, in 1995–1997. There were 3 women and 15 men, with a mean age at diagnosis of 57 years (range 44–72). Fourteen tumours were epithelial, two mixed, one fibromatous and one of undetermined subtype. Eight had previously been analysed by comparative genomic hybridization (CGH).
• Exposure: 13 of the 18 patients had a clear history of asbestos exposure. The article gives no fiber types, products, jobs or doses.
• Main results:
  • 10 of 18 tumours (56%) showed loss of heterozygosity or allelic imbalance with at least one marker at 14q
  • Partial deletions were more common than loss of the entire long arm. Deletion of all informative markers, indicating monosomy 14, was found in only one tumour (no. 18).
  • 14q11.1–q12 and 14q23–q24 were the most involved regions. The highest frequencies were at marker D14S972 (seven tumours; 50%) in 14q11.1–q12 and at marker D14S284 (six tumours; 60%) in 14q23–q24.
  • Eight of the ten tumours with losses had deletions at both 14q11.1–q12 and 14q23–q24
  • Among the eight tumours with earlier CGH data, results agreed except for tumour no. 2. That tumour showed deletions by allelotyping although its CGH profile had not passed the threshold for loss.
  • Patients whose tumours had 14q deletions had a median survival of 12 months; those without deletions had a median survival of 20 months
  • The survival difference between patients with and without 14q deletions was not statistically significant
  • 9 of 11 patients with stage 2 or 3 disease had 14q deletions, compared with 1 of 7 patients with stage 4 disease (P = 0.013, Fisher's exact test, two-tailed)
  • 14q deletions were found in 9 of 13 tumours from patients with a clear history of asbestos exposure and in 1 of 5 patients with no known exposure. This difference was not statistically significant.
• The authors' conclusion: The authors concluded that genomic losses at 14q are more frequent in mesothelioma than previously recognized by other methods. They added that the regions 14q11.1–q12 and 14q23–q24 provide a basis for further fine-mapping of genes that may be important in the development of malignant mesothelioma.
• Limitations the authors state:
  • The small number of samples does not allow decisive conclusions from the statistical analyses
  • Some findings scored as allelic imbalance rather than loss of heterozygosity may reflect tumour DNA being amplified more efficiently than normal DNA. For this reason the authors counted both as deletions.
  • Faint signals in tumour samples may come from contamination with normal cells or from variation within the tumour

Topics

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

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

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