Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report

Our plain-English summary of Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report, by K. Usuda, Y. Niida, M. Ishikawa, et al (Frontiers in Oncology, 2022).

The study

• Authors: K. Usuda, Y. Niida, M. Ishikawa, S. Iwai, A. Yamagata, Y. Iijima, N. Motono, S. Yamada, H. Uramoto
• Journal: Frontiers in Oncology
• Published: 2022;12:858094
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.

Copyright © 2022 Usuda, Niida, Ishikawa, Iwai, Yamagata, Iijima, Motono, Yamada and Uramoto.

In plain English

This case report from Kanazawa Medical University in Japan described one 77-year-old woman with no history of asbestos exposure, smoking, or radiation exposure. She was a housewife with no known contact with asbestos. Her right middle lung lobe was removed for a minimally invasive adenocarcinoma, stage IB. At 4 years and 7 months after surgery, a CT scan showed lung nodules, fluid around both lungs, and a right pleural tumor growing into the abdominal cavity. She died of respiratory failure within a month of that scan. An autopsy found a right malignant pleural mesothelioma of the sarcomatoid type that had invaded the right adrenal gland and the liver. Genetic testing found 50 somatic variants in the adenocarcinoma and 29 in the mesothelioma, and none were shared. Mutations in the TP53 and EP300 genes were found in the mesothelioma but not in the adenocarcinoma. The authors concluded that the two cancers arose independently. They hypothesized that the TP53 and EP300 mutations made the mesothelioma more aggressive. As a single case, it cannot show how often mesothelioma occurs without asbestos exposure.

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: case report (single patient), with genomic comparison of two tumors
• Who was studied: One 77-year-old woman treated by the authors' thoracic surgery department at Kanazawa Medical University, Japan; dates of treatment not given
• Exposure: No reported exposure: the patient had no history of asbestos exposure, smoking, or radiation exposure; she was a housewife in the country who did not work in a factory and had no known contact with asbestos
• Main results:
  • The first tumor was a minimally invasive lung adenocarcinoma (predominantly lepidic pattern), pT2aN0M0 (pStage IB), removed by right middle lobectomy and nodal dissection
  • At 2 years and 3 months after surgery, a right pleural effusion was found; its cytology was negative for malignancy
  • At 4 years and 7 months after surgery, chest CT showed multiple lung nodules, bilateral pleural effusion and a right pleural tumor invading the abdominal cavity
  • The patient died of respiratory failure within a month after that chest CT
  • Autopsy found a right malignant pleural mesothelioma, sarcomatoid type, invading the right adrenal gland and the liver
  • Staining of the mesothelioma was negative for lung markers and weakly positive for calretinin and positive for D2-40, which the authors read as mesothelial origin
  • Genetic sequencing found 50 somatic variants in the adenocarcinoma and 29 in the mesothelioma
  • No variants were shared between the two tumors, which the authors took to suggest different origins
  • TP53 and EP300 mutations were found in the mesothelioma but not in the adenocarcinoma
  • The mesothelioma did not have a BAP1 or CDKN2A mutation
  • Tumor mutation burden was 53.0 mut/Mbp in the adenocarcinoma and 30.7 mut/Mbp in the mesothelioma
  • Chromosome analysis showed abnormality in all chromosomes of the mesothelioma, but only relatively local abnormality in the adenocarcinoma
• The authors' conclusion: The authors concluded that the adenocarcinoma and the mesothelioma occurred independently, from different origins. They hypothesized that the TP53 and EP300 driver mutations made the mesothelioma more aggressive.
• Limitations the authors state:
  • The authors stated that they did not perform more detailed examinations at 4 years and 5 months after surgery that might have detected the new tumor
  • The research began after the patient's death, so her perspective could not be obtained

Topics

Medical terms in this study, explained in our Lexicon: Adenocarcinoma, Pleural Mesothelioma, Sarcomatoid, Asbestos Exposure, Bilateral, Pleural Effusion.

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