Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas

Our plain-English summary of Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas, by M. Ueda, R.M. Gemmill, J. West, et al (British Journal of Cancer, 2001).

The study

• Authors: M. Ueda, R.M. Gemmill, J. West, R. Winn, M. Sugita, N. Tanaka, M. Ueki, H.A. Drabkin
• Journal: British Journal of Cancer
• Published: 2001;85(1):64-8
• Cited by: 126 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the adenomatous polyposis coli (APC)/ beta-catenin/Tcf pathway in human tumorigenesis, there have been very few reports on mutations of the beta-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma cell lines for mutations in exon 3 of the beta-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the gamma-catenin gene. Mutational analysis for the entire coding region of beta-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical carcinoma cell lines. Deletion of most beta-catenin coding exons was confirmed in line NCI-H28 (lung mesothelioma) and a silent mutation at codon 214 in exon 5 was found in HeLa (cervical adenocarcinoma). A missense mutation at codon 19 and a silent mutation at codon 28 in the NH2-terminal regulatory region of the gamma-catenin gene were found in H1726 (squamous cell lung carcinoma) and H1048 (small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that beta- and gamma-catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian carcinomas.

Copyright 2001 Cancer Research Campaign.

In plain English

This was a laboratory study of human cancer cell lines grown in culture: 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma lines, 134 in all. It did not study asbestos or any other exposure. The authors looked for mutations in two genes, beta-catenin and gamma-catenin. They screened one region of each gene in every line, and the whole beta-catenin coding region in 20 lung, 9 breast, 5 kidney and 6 cervical lines. In NCI-H28, which the article calls a lung mesothelioma line, part of the beta-catenin gene was missing on both copies, and no beta-catenin message was detected. HeLa, a cervical adenocarcinoma line, had a silent beta-catenin change at codon 214, meaning the protein was unchanged. For gamma-catenin, only two of the 134 lines showed mutations. NCI-H1726 (squamous cell lung carcinoma) had a missense change at codon 19, which the authors called potentially activating. NCI-H1048 (small cell lung carcinoma) had a silent change at codon 28. The authors concluded that these genes may not be frequent mutation targets in these cancers. They said the effects of the NCI-H28 deletion are unknown.

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 human cancer cell lines (mutation screening of the beta- and gamma-catenin genes by PCR, SSCP analysis and sequencing)
• Who was studied: 134 human carcinoma cell lines (93 lung, 9 breast, 6 kidney, 19 cervical, 7 ovarian), obtained from the American Type Culture Collection and from Japanese institutes; the whole beta-catenin coding region was checked in 20 lung, 9 breast, 5 kidney and 6 cervical lines
• Exposure: No asbestos or other exposure was studied; the study examined genes in cancer cell lines
• Main results:
  • In beta-catenin exon 3, no point mutations were found in any of the cell lines, but a homozygous deletion was confirmed in NCI-H28 (described as lung mesothelioma)
  • No beta-catenin message could be amplified from NCI-H28, which the authors interpreted as the message either not being made or being rapidly degraded
  • HeLa (cervical adenocarcinoma) had a silent beta-catenin mutation at codon 214 in exon 5 that did not change the amino acid
  • Apart from NCI-H28 and HeLa, no beta-catenin alteration outside exon 3 was found in the other 38 cell lines whose full coding region was examined
  • Of 134 cell lines, only two had gamma-catenin mutations: a missense mutation at codon 19 (Thr to Ile) in NCI-H1726 (squamous cell lung carcinoma) and a silent mutation at codon 28 in NCI-H1048 (small cell lung carcinoma)
  • The authors described the NCI-H1726 gamma-catenin mutation as the only potentially activating mutation found
• The authors' conclusion: The authors concluded that beta- and gamma-catenin may not be frequent targets of mutation in the development of human lung, breast, kidney, cervical and ovarian carcinomas
• Limitations the authors state:
  • The authors stated that the effects of the beta-catenin deletion in NCI-H28 are unknown and need further study

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Carcinogenesis, Mesothelioma, Adenocarcinoma, Squamous Cell Carcinoma.

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