Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing

Our plain-English summary of Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing, by N. Oumi, H. Itamochi, H. Komatsu, et al (Human Cell, 2016).

The study

• Authors: N. Oumi, H. Itamochi, H. Komatsu, T. Oishi, M. Shimada, S. Sato, J. Chikumi, S. Sato, M. Nonaka, A. Kudoh, T. Harada
• Journal: Human Cell
• Published: 2016;29(1):46-51
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A new cell line of human malignant peritoneal mesothelioma (MPM), TU-MM-1, was established and characterized. The cells showed polygonal morphology, grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle. The chromosome numbers ranged from 41 to 44. A low rate of proliferation was observed and the doubling time was 67.9 h. Genomic DNA sequencing revealed that TU-MM-1 cells harbored missense mutations in APC, LATS2, BRCA1/2, and TP53, and mutation of a splice donor site in BAP1 and loss of CDKN2A gene. We observed the absence of BAP1 and p16(INK4a) proteins, underexpression of LATS2 protein, and overexpression of p53 protein in TU-MM-1 cells in western blot analysis. Heterotransplantation to nude mice produced tumors that had the characteristics of the original tumor. This cell line may be useful for studying biological properties and contribute to novel treatment strategies.

In plain English

This laboratory study created a new cell line, called TU-MM-1, from one patient's epithelioid malignant peritoneal mesothelioma. The patient, a 51-year-old Japanese woman operated on in 2014, had no history of asbestos exposure. Her mother died of malignant pleural mesothelioma, also with no history of asbestos exposure. The cells grew slowly, doubling in 67.9 hours on average. Their chromosome numbers ranged from 41 to 44. Gene sequencing of the cells found mutations in APC, LATS2, BRCA1, BRCA2, TP53 and BAP1, and the CDKN2A gene was not detected. No mutations were seen in NF2, CUL1, PIK3CA or EGFR. The BAP1 and p16INK4a proteins were not detected in the cells. Compared with HeLa cells, LATS2 protein was lower and p53 protein was higher. Cells injected into nude mice formed 5-mm tumors after 28 days, and these tumors resembled the original tumor. The authors suggested that BRCA1/2 might be tumor suppressor genes in this cancer. They noted that they could not test the original tumor, or the patient's or her mother's inherited genes, for these mutations.

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 study establishing and characterizing a cell line from one patient's tumor (cell growth, chromosome analysis, whole exome and whole genome sequencing, western blot, and transplantation into nude mice)
• Who was studied: Tumor cells from one 51-year-old Japanese woman with epithelioid malignant peritoneal mesothelioma who had surgery (omentectomy) in 2014; female BALB/c nude mice were used for transplantation
• Exposure: No asbestos exposure was studied; the patient had no history of exposure to asbestos, and her mother, who died of malignant pleural mesothelioma, also had no history of asbestos exposure
• Main results:
  • The TU-MM-1 cells grew slowly, with an average doubling time of 67.9 hours (standard deviation 8.8 hours)
  • Chromosome numbers in TU-MM-1 cells ranged from 41 to 44, with a most common number of 42
  • Sequencing of the cell line found missense mutations in APC, LATS2, BRCA1/2 and TP53, and a splice donor site mutation in BAP1
  • No mutations were found in NF2, CUL1, PIK3CA or EGFR, and the CDKN2A gene was not detected in the cell line
  • BAP1 and p16INK4a proteins were not detected in TU-MM-1 cells
  • Compared with HeLa cells, TU-MM-1 cells had markedly lower LATS2 protein and higher p53 protein
  • Injected into nude mice, the cells produced 5-mm-diameter tumors after 28 days
  • Both the original tumor and the mouse tumors stained positive for the mesothelioma marker calretinin
• The authors' conclusion: The authors suggested that BRCA1/2 might be tumor suppressor genes for malignant peritoneal mesothelioma and could be treatment targets. They hoped the cell line would be useful for studying the disease's biology and finding new treatments.
• Limitations the authors state:
  • The authors could not check for BRCA1/2 mutations in the original tumor, or for inherited (germline) mutations in the patient and her mother, so further studies are needed

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, BAP1, CDKN2A.

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