Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes

Our plain-English summary of Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes, by W.L. Flejter, F.P. Li, K.H. Antman, et al (Genes, Chromosomes & Cancer, 1989).

The study

• Authors: W.L. Flejter, F.P. Li, K.H. Antman, J.R. Testa
• Journal: Genes, Chromosomes & Cancer
• Published: 1989;1(2):148-54
• Cited by: 93 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cytogenetic analysis was performed on short-term cultures of primary tumor tissue obtained from five patients with pleural malignant mesothelioma. Clonal karyotypic abnormalities were detected in four patients, none of whom had received cytotoxic therapy prior to karyotypic evaluation. Recurring chromosomal changes included partial deletions of 1p and 3p, and monosomy of 18, 19, and 22. We also reviewed data on 24 previously reported pretreatment patients and determined that alterations of chromosomes 1, 3, and 22 are frequently associated with malignant mesothelioma. Partial loss of chromosome 1 due to deletions or other rearrangements most frequently involve bands 1p11-pter with the shortest region of overlap (SRO) occurring at 1p21-p22 in our patients. Deletions and other structural changes of chromosome 3 usually involve the region 3p14-p25. The SRO of 3p deletions appeared to be at band 3p21. Monosomy 22 represents the most consistent specific whole chromosome loss seen in malignant mesothelioma, being observed in 11 of 28 cases summarized. In addition, structural changes of 22q have been observed in three patients, and a breakpoint at 22q11 was reported in each case. Taken collectively, these data suggest that a cascade of events involving alterations of genes on more than one specific chromosome may play a critical role in the development of malignant mesothelioma. The pattern of recurring chromosomal loss, particularly of 1p, 3p, and 22q, indicates that these regions should be targeted for future molecular investigations into the possible involvement of suppressor genes in this malignancy.

In plain English

This study examined the chromosomes of tumor cells from five patients with pleural malignant mesothelioma: one woman and four men, aged 43 to 59. Four patients reported past asbestos exposure at work. For the fifth, exposure was unknown. Tumor samples were grown briefly in the laboratory and their chromosomes were examined. Tumors from four patients showed repeated (clonal) chromosome abnormalities. The fifth patient, who had received extensive prior chemotherapy, showed no distinct abnormal clone. In all four tumors with clones, chromosomes 1 and 3 were altered, and three of the four had abnormalities of chromosome 22. The authors then combined their four cases with 24 previously reported cases examined before treatment. Across these 28 cases, partial loss of the short arm of chromosome 1 (1p) was seen in 17 (61%), abnormalities of 3p in 16 (57%), and abnormalities of chromosome 22 in 16 (57%). Most of the chromosome 22 changes (11 of 16) were loss of a whole copy. The authors noted their study was small. They concluded that regions 1p, 3p and 22q should be targeted in future research into possible tumor suppressor genes in this cancer.

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 chromosome (cytogenetic) analysis of tumor samples from five patients, combined with a review of 24 previously reported cases
• Who was studied: Five patients with primary pleural malignant mesothelioma, one female and four male, aged 43 to 59. Separately, 24 previously reported patients examined before treatment, giving 28 cases with clonal abnormalities in the combined analysis.
• Exposure: Four of the five patients reported prior occupational asbestos exposure. For the fifth, exposure was unknown. No fiber types or doses were given.
• Main results:
  • Clonal chromosome abnormalities were found in four of the five patients, none of whom had received cytotoxic therapy before testing.
  • Patient 017, who had received extensive prior cytotoxic therapy, had scattered non-clonal changes but no distinct abnormal clone.
  • Among the four patients with clonal changes, chromosome 1 was abnormal in all four. The shortest region of overlap of the deleted segments was at bands 1p21 to 1p22.
  • Among the four patients with clonal changes, structural changes of chromosome 3 were found in all four.
  • Among the four patients with clonal changes, three had abnormalities of chromosome 22.
  • Among the four patients with clonal changes, three had monosomy (loss of one copy) of chromosome 18. Two had monosomy 19, and a third had a rearrangement involving 19q.
  • Patient 067 was the only patient with an abnormal clone who had two apparently normal copies of chromosome 22. This patient was also the only one with a biphasic tumor.
  • In the combined 28 cases with clonal abnormalities (four from this study, 24 previously reported), losses of 1p were seen in 17 patients (61%).
  • In the combined 28 cases, abnormalities of 3p were seen in 16 (57%).
  • In the combined 28 cases, chromosome 22 abnormalities were seen in 16 (57%). Of these 16, 11 were monosomy.
• The authors' conclusion: The authors concluded that the recurring loss of parts of chromosomes 1p, 3p and 22q indicates that these regions should be targeted in future molecular research into possible tumor suppressor genes in malignant mesothelioma. They noted that some changes, such as those of chromosomes 1 and 3, may be secondary changes associated with tumor progression.
• Limitations the authors state:
  • The study was small and no clinical correlations could be made.
  • Differences in deleted regions between studies may reflect difficulty assigning breakpoints in tumor chromosomes, which often show poor banding.
  • In case 043, parts of chromosome 22 may have been present in unidentified marker chromosomes, so its apparent loss of both copies is uncertain.

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, Tumor Suppressor Gene.

Related studies

• Chromosome 3 and 12p rearranged in a well-differentiated peritoneal mesothelioma — H.J. Decker, F.P. Li, et al. (1990)
• Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma: correlation between Southern blot and cytogenetic analyses — M. Tiainen, J. Kere, et al. (1992)
• Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma — S.S. Murthy, J.R. Testa (1999)
• Translocation (3;3)(p14;q29) as the primary chromosome abnormality in a peritoneal mesothelioma — M.R. Teixeira, K.E. Giercksky, et al. (1998)
• Loss of heterozygosity of chromosome 3p21 is associated with mutant TP53 and better patient survival in non-small-cell lung cancer — C.J. Marsit, M. Hasegawa, et al. (2004)
• LATS2 is a tumor suppressor gene of malignant mesothelioma — H. Murakami, T. Mizuno, et al. (2011)

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