Absence of post-transcriptional RNA modifications of BCL10 in human malignant mesothelioma and colorectal cancer

Our plain-English summary of Absence of post-transcriptional RNA modifications of BCL10 in human malignant mesothelioma and colorectal cancer, by S. Apostolou, S.S. Murthy, P. Kolachana, et al (Genes, Chromosomes & Cancer, 2001).

The study

• Authors: S. Apostolou, S.S. Murthy, P. Kolachana, S.C. Jhanwar, J.R. Testa
• Journal: Genes, Chromosomes & Cancer
• Published: 2001;30(1):96-8
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The BCL10 gene, located at 1p22, has been implicated in a number of human malignancies, including malignant mesotheliomas (MMs) and colorectal carcinomas. Subsequent reports, however, have revealed an absence of BCL10 mutations in genomic DNA from such tumors. It has been proposed that some abnormalities of this gene may be found only in RNA and not in genomic DNA, suggesting that BCL10 may be mutated post-transcriptionally, rather than at the genomic level. To explore this possibility, we performed SSCP mutation analysis and direct sequencing of cDNA from 17 MM cell lines displaying LOH in 1p22, 12 MM tumor specimens, and 11 colon carcinoma cell lines. SSCP revealed several different band shifts in these samples. The nucleotide changes observed in the cDNA samples were also seen in matched genomic DNA and corresponded to known polymorphisms in the general population. Thus, we conclude the BCL10 mutations are absent at the cDNA level, and that this gene does not undergo "molecular misreading." Since BCL10 also does not possess mutations at the genomic DNA level, it can be ruled out as a gene involved in the pathogenesis of MM and colorectal cancer.

In plain English

This short laboratory report tested whether the BCL10 gene, found on chromosome region 1p22, shows changes in its RNA (studied as cDNA, a DNA copy of RNA) in malignant mesothelioma and colon cancer. The authors screened cDNA from 17 malignant mesothelioma cell lines showing loss of heterozygosity (LOH) at 1p22, 12 malignant mesothelioma tumor specimens and 11 colon carcinoma cell lines. They used a screening method called SSCP followed by direct sequencing, with a normal mesothelial cell line as a comparison. Screening found a variant pattern in exon 1 in 12 of the 17 mesothelioma cell lines, but the same pattern appeared in the normal mesothelial cells. Sequencing found two kinds of DNA change. In the mesothelioma cell lines, both were also present in genomic DNA and had previously been identified as polymorphisms (known variants) in the general population. The study did not examine asbestos exposure. The authors concluded that BCL10 mutations are absent at the cDNA level and that the gene can be ruled out as involved in the development of several types of malignancy.

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 molecular genetic study (brief communication): mutation screening (SSCP) and direct sequencing of BCL10 cDNA from tumor cell lines and tumor samples
• Who was studied: 17 malignant mesothelioma cell lines showing loss of heterozygosity (LOH) at 1p22, 12 malignant mesothelioma tumor specimens and 11 colon carcinoma cell lines, plus a normal mesothelial cell line as a control. The article does not state where the samples came from or when they were collected.
• Main results:
  • Variant exon 1 bands were seen in 12 of the 17 malignant mesothelioma cell lines, and the same band pattern was seen in the normal mesothelial cell sample
  • In 2 malignant mesothelioma cell lines, the exon 3 product showed a band pattern different from normal mesothelial cells
  • Band shifts seen in cDNA from the mesothelioma cell lines were also found in genomic DNA from the same cell lines
  • The patterns in the 12 malignant mesothelioma tumor samples were identical to those in the mesothelioma cell lines
  • In the 11 colon carcinoma cell lines, variant exon 1 bands were seen in 2 lines. No variant bands were seen for exon 2 in any sample.
  • One nucleotide change was in exon 3 (position 638, G to A). It was predicted to change glycine to glutamic acid at position 213. It was found in mesothelioma cell lines 10 and 17, mesothelioma tumors T10 and T25, and colorectal samples 9 and 13. The other change was in exon 1 (position 24, G to C) and did not change the amino acid.
  • The changes found in mesothelioma cDNA were also present in genomic DNA from the same cell lines. They had previously been identified as polymorphisms in the general population.
  • The exon 1 change occurred at a similar frequency in the general population. The authors judged it likely that this polymorphism does not increase predisposition to mesothelioma or colon carcinoma.
  • None of the BCL10 alterations reported in earlier studies were found in the mesothelioma or colon carcinoma samples
• The authors' conclusion: The authors concluded that BCL10 mutations are absent at the cDNA level and that the gene does not undergo 'molecular misreading'. Because the gene also lacks mutations in genomic DNA, they concluded it can be ruled out as a gene involved in the development of several types of malignancy.
• Limitations the authors state:
  • The authors state it remains to be determined whether BCL10 might act through loss of a single copy (haplo-insufficiency)

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Colorectal Cancer, Carcinoma.

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