p16/CDKN2 gene and p53 gene alterations in Japanese non-smoking female lung adenocarcinoma

Our plain-English summary of p16/CDKN2 gene and p53 gene alterations in Japanese non-smoking female lung adenocarcinoma, by Y. Takeshima, T. Nishisaka, R. Kawano, et al (Japanese Journal of Cancer Research, 1996).

The study

• Authors: Y. Takeshima, T. Nishisaka, R. Kawano, K. Kishizuchi, S. Fujii, S. Kitaguchi, K. Inai
• Journal: Japanese Journal of Cancer Research
• Published: 1996;87(2):134-40
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Primary lung adenocarcinomas in non-smoking females are increasing in the USA and Japan. Environmental factors such as passive smoking, asbestos, domestic radon, and hormonal effects have been implicated, but the etiology is still uncertain. We therefore analyzed point mutations of p16 gene, a newly characterized tumor suppressor gene, and compared the results with alterations of p53 gene in 28 primary lung adenocarcinomas in non-smoking Japanese females. There were no cases with somatic point mutation of p16 gene, except for one case with two germline mutations (silent mutations). In contrast, six out of 16 informative cases showed loss of heterozygosity of p53 gene using a TP53 microsatellite marker and 19 out of 28 cases showed expression of oncoprotein using DO-7 immunohistochemistry. These findings suggest that p16 gene alteration is a rare event in primary lung adenocarcinomas in Japanese non-smoking females, compared with alterations of the p53 gene.

In plain English

This laboratory study examined genetic changes in lung tumors from 28 Japanese women who did not smoke and had primary lung adenocarcinoma in 1992–1994. The tissue came from the pathology files of Hiroshima University School of Medicine. The article mentions asbestos only as one suspected cause of such cancers. It states that precise details on passive smoking and on environmental and occupational exposure to specific carcinogens were not available. Of 20 cases examined, none showed tumor-specific point mutations in the p16 gene. One woman carried two silent changes found in both her tumor and her normal tissue. Two cases showed loss of a chromosome region near p16. By contrast, 6 of 16 informative cases showed loss of the p53 gene region, and 19 of 28 tumors stained for p53 protein. The authors concluded that p16 alteration is rare in these cancers compared with p53 alterations. They noted that normal cells could not be fully removed from the samples and that homozygous deletions of the p16 gene could not be excluded.

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-pathology study of archived tumor and normal tissue (gene mutation, loss of heterozygosity and immunohistochemistry analyses)
• Who was studied: 28 non-smoking Japanese women with primary lung adenocarcinoma, cases from 1992–1994, from the files of the Department of Pathology, Hiroshima University School of Medicine, Japan
• Exposure: Exposure was not a subject of the analyses. Asbestos is mentioned only in the introduction as one suspected cause. Precise details on passive smoking and on environmental and occupational exposure to specific carcinogens were not available
• Main results:
  • Of the 20 cases examined by PCR-SSCP, none showed abnormal bands in exon 1 or in the first and last regions of exon 2 of the p16 gene
  • One case (FT8) had two silent changes in the p16 gene, present in both tumor and non-neoplastic tissue (germline)
  • Loss of heterozygosity near the p16 gene (9p21-22) was found in one case at the IFNA marker (FT4) and in another at D9S171 (FT17)
  • At the TP53 marker, 6 of 16 informative cases showed loss of heterozygosity of the p53 gene region
  • 19 of 28 cases showed p53 protein expression by DO-7 immunohistochemistry
• The authors' conclusion: The authors concluded that alteration of the p16 gene is a rare event in primary lung adenocarcinomas of non-smoking Japanese women compared with p53 alterations, and that other target genes need to be analyzed
• Limitations the authors state:
  • Non-neoplastic cells could not be completely excluded from the dissected tumor samples
  • Homozygous deletions of the p16 gene could not be excluded; further Southern blot analysis is needed
  • The germline changes in case FT8 may be either a new disease-associated mutation or a rare polymorphism
  • p53 immunohistochemistry does not always reflect p53 gene alterations, so sequence analysis of the p53 gene is needed
  • Precise details on passive smoking and on environmental and occupational exposure to specific carcinogens were not available

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 Adenocarcinoma, Etiology, Tumor Suppressor Gene, Germline Mutation, Immunohistochemistry.

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