Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing

Our plain-English summary of Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing, by S. Zhang, Q. Zhang, Q. Sun, et al (Cellular Physiology and Biochemistry, 2018).

The study

• Authors: S. Zhang, Q. Zhang, Q. Sun, J. Tang, J. Chen, N. Ji, Y. Zheng, F. Fang, W. Lei, P. Li, N. Zhang
• Journal: Cellular Physiology and Biochemistry
• Published: 2018;45(1):163-174
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background/aims: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown.

Methods: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient.

Results: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis revealed a parallel evolution of the tumor in this patient. We also identified some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2.

Conclusions: The results showed a comprehensive genomic change in malignant mesothelioma of the tunica vaginalis testis and provide a better understanding of the clonal evolution during tumor recurrence and metastasis.

© 2018 The Author(s). Published by S. Karger AG, Basel.

In plain English

This was a genetic study of one patient: a 65-year-old Chinese man with malignant mesothelioma of the tunica vaginalis testis, the lining around the testis. The article reports that he denied any history of asbestos exposure. The authors read the whole genome (the full DNA) of four tumor samples removed in successive surgeries and compared them with his blood. Two samples came from the left testis and two from lymph nodes in the left groin. All four tumor samples had extra copies of parts of chromosomes 1 and 12. The number of single-letter DNA changes ranged from 758 to 1628 per sample, and 119 changes were shared by all four. A family-tree analysis suggested that one groin tumor arose from the original tumor and the other from the first recurrence. A changed gene called KIF25 was found in all four samples. No mutations were found in genes frequently mutated in pleural mesothelioma, such as BAP1, NF2 and TP53. The authors suggested this tumor type has its own genetic features. They noted that only one case was studied.

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: Single-patient genomic case study: whole-genome sequencing of four successive tumor samples and one blood sample
• Who was studied: One 65-year-old Chinese man treated at the Second Affiliated Hospital, Zhejiang University School of Medicine, China, with malignant mesothelioma of the tunica vaginalis testis. The primary tumor and the first recurrence came from his left testis. The two later samples came from left inguinal (groin) lymph nodes.
• Exposure: No asbestos exposure was reported; the patient denied a history of asbestos exposure
• Main results:
  • 1328, 1628, 838 and 758 single-nucleotide variants were found in tumor samples CA08, CA14E, CA14L and CA15 respectively; 119 were shared by all tumor samples
  • All tumor samples had amplified copy number changes in chromosomes 1 and 12
  • Later recurrent and metastatic tumors showed gradually decreasing rates of C-to-T mutations
  • The phylogenetic analysis suggested that sample CA14L (groin) probably originated from the primary tumor (CA08), and that the latest lesion (CA15) more likely evolved from the first recurrence in the testis (CA14E)
  • Among the significantly mutated genes identified, a KIF25 mutation was found in all four tumor samples
  • Seven missense mutations were found in cancer-related genes in the patient's blood cells (leukocytes); none of these genes had previously been reported as predisposing genes for mesothelioma
  • No mutations were detected in genes frequently mutated in malignant pleural mesothelioma, such as BAP1, NF2, TP53, SETD2 and DDX3X
• The authors' conclusion: The authors concluded that they identified a particular pattern of evolution in this tumor type and some genes that might be important for mesothelioma development and progression. They suggested that testicular mesothelioma has genetic characteristics different from malignant pleural mesothelioma.
• Limitations the authors state:
  • Only one case was studied; it is unclear whether the conclusions apply to other patients
  • DNA came from formalin-fixed paraffin-embedded samples rather than fresh or frozen tissue
  • The effects of the mutations on gene transcripts and protein function were not investigated
  • Circulating tumor cells were not considered

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: Malignant Mesothelioma, Tunica Vaginalis, Mesothelioma, Metastasis.

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