Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis

Our plain-English summary of Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis, by A. Kowalik, A. Wincewicz, S. Zięba, et al (Polish Journal of Pathology, 2020).

The study

• Authors: A. Kowalik, A. Wincewicz, S. Zięba, W. Baran, J. Kopczyński, M. Koda, S. Sulkowski, S. Goźdź
• Journal: Polish Journal of Pathology
• Published: 2020;71(1):69-74
• Type of article: Case report
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285T<C p.V762A), RNF213 (NM_001256071: c.3121G<A, p.A1041T), PAX8 (NM_013992: c.404A>G, p.K135R), MTRR (NM_024010: c.147A>G, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.

In plain English

This case report described one 81-year-old man. His testis, epididymis, testicular coverings and part of the spermatic cord were removed because of a fluid collection around the testis (hydrocele). The tissue showed many finger-like tumor growths on the lining around the testis (the tunica vaginalis), with local invasion of the rete testis. The tumor was diagnosed as malignant mesothelioma, epithelioid type, of the tunica vaginalis. The authors tested 409 cancer-related genes and found six mutations in five genes: PARP1, RNF213, PAX8, MTRR and two in KMT2C. Four were classified as benign polymorphisms and two, in PAX8 and KMT2C, as pathogenic. The authors noted that the PAX8 change had been flagged as a SNP (a known DNA variant) and excluded from the COSMIC cancer database. They could not judge with high confidence whether CDKN2A was deleted, but they suspected both copies were lost. The authors concluded that this profile differed from that described in pleural mesothelioma. They noted the limits of a single case. The article does not report whether this patient was exposed to asbestos.

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 immunohistochemistry and next-generation sequencing of 409 cancer-related genes
• Who was studied: one 81-year-old man with malignant mesothelioma of the tunica vaginalis testis, treated in Poland (author affiliations in Kielce, Checiny and Bialystok); dates not given
• Exposure: The article does not report any asbestos or other exposure history for this patient. Its introduction cites other studies linking these tumors to asbestos.
• Main results:
  • The tumor was diagnosed as malignant mesothelioma, epithelioid type, of the testicular vaginal tunica (stage pT2).
  • The tumor stained positive for WT-1, CKAE1/AE3, calretinin and CK7, and negative for CK5, PSA, TTF-1 and mucicarmine.
  • Necrosis occupied 15% of the tumor tissue.
  • The mitotic rate averaged 25 mitoses per 10 high-power fields.
  • The tumor locally invaded the rete testis, without apparent extension beyond the parietal lamina.
  • Sequencing detected six mutations in five genes: PARP1, RNF213, PAX8, MTRR, and two in KMT2C.
  • Four mutations were classified as benign polymorphisms (PARP1 p.V762A, RNF213 p.A1041T, MTRR p.I49M, KMT2C p.Y816fs). Two were classified as pathogenic (PAX8 p.K135R and KMT2C p.D348N).
  • The PAX8 mutation, classified as pathogenic by bioinformatic analysis, had been flagged as a SNP and excluded from the COSMIC database.
  • Very low sequencing depth at the CDKN2A and CDKN2B locus led the authors to suspect that both CDKN2A alleles were lost.
• The authors' conclusion: The authors concluded that the mutations in this case differed from the profile of mutated genes described in malignant pleural mesothelioma. They suggested that malignant transformation might be related to the tumor's anatomical location, and that the detected mutations could be a basis for future targeted therapies.
• Limitations the authors state:
  • The report is a single case study.
  • The authors could not assess homozygous deletion of CDKN2A with high confidence.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Tunica Vaginalis, Necrosis, Calretinin, Thyroid Transcription Factor-1 (TTF-1).

Related studies

• Malignant mesothelioma of testicular tunica vaginalis — K. Abe, N. Kato, et al. (2002)
• Imaging of mesothelioma of tunica vaginalis testis — M. Bertolotto, I. Boulay-Coletta, et al. (2016)
• Mesothelioma of the tunica vaginalis testis — K.J. Butnor, E.N. Pavlisko, et al. (2019)
• Mesothelioma of tunica vaginalis testis and asbestos exposure — C. Mensi, M. Pellegatta, et al. (2012)
• Mesothelioma of the tunica vaginalis testis: report of 2 cases with asbestos occupational exposure — G. Gorini, M. Pinelli, et al. (2005)
• Fine needle aspiration cytology in malignant mesothelioma of the tunica vaginalis testis — R. Gupta, P. Dey, et al. (2011)

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