Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma

Our plain-English summary of Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma, by T. Naka, Y. Hatanaka, K. Marukawa, et al (Diagnostic Pathology, 2016).

The study

• Authors: T. Naka, Y. Hatanaka, K. Marukawa, H. Okada, K.C. Hatanaka, J. Sakakibara-Konishi, S. Oizumi, Y. Hida, K. Kaga, T. Mitsuhashi, Y. Matsuno
• Journal: Diagnostic Pathology
• Published: 2016;11:38
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.

Methods: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).

Results: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.

Conclusion: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.

In plain English

This case report described one patient: a 77-year-old Japanese man with a 20-pack-year smoking history who had been exposed to asbestos while working in the construction industry between the ages of 40 and 65. Surgery removing the left lung and pleura found two separate tumors that met within the left lower lobe. One was an epithelioid-type malignant pleural mesothelioma and the other a primary pulmonary adenocarcinoma. Asbestos bodies were found in non-tumorous lung tissue. The authors compared DNA copy number changes and gene mutations in the two tumors. The mesothelioma showed loss at 9p21.2-3, which the authors describe as a common change in mesothelioma, and an ATM mutation. The adenocarcinoma showed copy number gains more often than losses. It had no changes at 2p16, 9q33.1 or 19p13, regions earlier reported in asbestos-associated lung cancer, but had some changes previously linked to smoking. The authors concluded that in this particular case asbestos exposure may not have played a primary role in the adenocarcinoma, and that smoking may have contributed more to its copy number gains. They noted that no conclusive evidence is possible from this case alone.

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 with genetic analysis (DNA copy number by SNP array and targeted next-generation sequencing) of two tumors from one patient
• Who was studied: one 77-year-old Japanese man with a 20-pack-year smoking history, treated at Hokkaido University Hospital, Japan, who had a collision tumor of malignant pleural mesothelioma (epithelioid type) and primary pulmonary adenocarcinoma in the left lower lobe
• Exposure: occupational asbestos exposure in the construction industry between ages 40 and 65 (fiber type not stated), plus 20 pack-years of cigarette smoking; asbestos bodies were detected in non-tumorous lung tissue
• Main results:
  • The mesothelioma showed copy number loss at 9p21.2-3 and in several regions of the long arm of chromosome 6, which the authors describe as common alterations in mesothelioma. It also showed copy number gain across almost all of chromosome 8.
  • In the mesothelioma, gene alterations at 22q12.2 and 17p13.1 were not detected.
  • The mesothelioma had a somatic ATM mutation (G2706A). Possible germline mutations of TP53 (P72R) and KDR (Q472H) were found in both tumors, at mutation rates of almost 50%.
  • In the adenocarcinoma, copy number gain occurred more frequently than loss. Loss and copy-neutral loss of heterozygosity were rarely found.
  • The adenocarcinoma had no detectable alterations at 2p16, 9q33.1 or 19p13, which have been reported previously in asbestos-associated lung cancer.
  • Some copy number alterations previously reported as associated with smoking were found in the adenocarcinoma.
  • The adenocarcinoma had somatic mutations of ERBB4 (300 fs, 301 fs) and STK11 (E65G). Testing was negative for EGFR, KRAS/NRAS/BRAF mutations and ALK fusion protein.
  • Neither tumor had any copy number alteration on chromosome 16 or 21.
• The authors' conclusion: The authors concluded that in this particular case asbestos exposure may not have played a primary role in the development of the adenocarcinoma, and that cigarette smoking may have contributed more to its copy number gains.
• Limitations the authors state:
  • The authors stated that no conclusive evidence about how different carcinogens affect different thoracic tumor types is possible from this single case.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Adenocarcinoma, Asbestos Exposure, Somatic Mutation, Histology, Next-Generation Sequencing (NGS), Lung Cancer, Mesothelioma.

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