Genetic Landscape of a Pleural Mesothelioma in a Child Affected by NF2-Related Schwannomatosis

Our plain-English summary of Genetic Landscape of a Pleural Mesothelioma in a Child Affected by NF2-Related Schwannomatosis, by M. Ognibene, G. Piccolo, M. Crocco, et al (International Journal of Molecular Sciences, 2025).

The study

• Authors: M. Ognibene, G. Piccolo, M. Crocco, M. Di Duca, A. Verrico, M. Molteni, F. Romano, V. Capra, A. Rossi, F. Zara, P. De Marco, C. Milanaccio
• Journal: International Journal of Molecular Sciences
• Published: 2025;26(14)
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We report the first case of pleural mesothelioma (PM) occurring in a child affected by NF2-related schwannomatosis (NF2-SWN) and without any history of environmental exposure to asbestos. Mesothelioma is a rare secondary tumor in brain cancer patients and the association with NF2-SWN has been described only in a few anecdotal cases and never in the pediatric field. NF2-SWN is an autosomal dominant disease caused by inactivating germline mutations of the NF2 tumor suppressor gene, one of the most common mutations associated with human primary mesothelioma too. By MLPA assay, array-CGH analysis, and NGS on blood and tumor DNA, we determined the mutation profile of this rare NF2-driven PM and we identified several atypical chromosomal aberrations in tumor cells, suggesting a different genomic signature between pediatric and adult mesothelioma.

In plain English

This case report described a boy diagnosed at one year of age with severe NF2-related schwannomatosis, a genetic condition that causes nervous system tumors. Twelve years later, at age 13, he developed epithelioid pleural mesothelioma. The authors reported no environmental exposure to asbestos and no family history of tumors. A blood test found a germline deletion, present in the body's non-tumor cells, in one copy of the NF2 gene. In tumor cells taken from fluid around the lung, the authors found loss of the whole chromosome 22, which carries NF2, so both copies of NF2 were inactivated. The tumor also had extra copies of whole chromosomes 6, 10, 11, 16 and 20 and had lost whole chromosomes 14, 22 and Y. A 501-gene cancer panel found no disease-causing single-letter DNA changes (single-nucleotide variants) in cancer-related genes. The authors noted that, apart from the losses of chromosomes 14 and 22, these changes are not typical of mesothelioma. The mesothelioma followed a mild course, and he died about one year later from rapidly growing meningiomas. The authors suggested that the tumor's genetic profile may differ from adult mesothelioma.

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 (genetic analysis of one patient's blood and tumor DNA)
• Who was studied: one boy, diagnosed with severe NF2-related schwannomatosis at age one, who developed pleural mesothelioma twelve years later, at age 13
• Exposure: no asbestos exposure reported. The factor studied was genetic: a germline NF2 gene deletion found in blood, followed by loss of NF2 in the tumor
• Main results:
  • In the patient's blood DNA, MLPA testing found a heterozygous deletion of the NF2 gene covering the 5'UTR and exon 1, confirming the clinical diagnosis
  • The mesothelioma was epithelioid and followed a mild course, with overall survival of about one year. The patient died because of rapidly increasing meningiomas
  • Array-CGH on tumor (effusion) cells showed gain of whole chromosomes 6, 10, 11, 16 and 20 and loss of whole chromosomes 14, 22 and Y
  • NGS of tumor DNA with a 501-gene cancer panel found no pathogenic single-nucleotide variants in cancer-related genes, but confirmed the copy number changes and the somatic loss of the NF2 locus
  • Ten cancer-related genes besides NF2 (PARP2, FANCM, RAD51B, MLH3, DICER1, XRCC3, MAPK1, SMARCB1, CHEK2, EP300) were among the copy number losses on chromosomes 14 and 22. The authors said the link of their loss to pleural mesothelioma is not yet clearly proven
  • Apart from the losses of chromosomes 14 and 22, the chromosomal changes found are not typical of mesothelioma, according to the authors
• The authors' conclusion: The authors concluded that this first known pediatric case of NF2-related schwannomatosis with pleural mesothelioma suggests a possibly different genomic signature from adult mesothelioma. They also proposed that NF2 inactivation may be an early driver event in pediatric mesothelioma, and said further studies are needed

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Environmental Exposure, Mesothelioma, Germline Mutation, Tumor Suppressor Gene.

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