Analysis of the neurofibromatosis type 2 gene in different human tumors of neuroectodermal origin

Our plain-English summary of Analysis of the neurofibromatosis type 2 gene in different human tumors of neuroectodermal origin, by L.R. De Vitis, A. Tedde, F. Vitelli, et al (Human Genetics, 1996).

The study

• Authors: L.R. De Vitis, A. Tedde, F. Vitelli, F. Ammannati, P. Mennonna, P. Bono, B. Grammatico, P. Grammatico, P. Radice, U. Bigozzi, E. Montali, L. Papi
• Journal: Human Genetics
• Published: 1996;97(5):638-41
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The autosomal dominant syndrome neurofibromatosis type 2 (NF2) is characterized by the development of bilateral vestibular schwannomas, meningiomas, ependymomas and gliomas. The NF2 gene, recently isolated from chromosome 22, is mutated in both sporadic and NF2 tumors such as schwannomas, meningiomas and ependymomas. Mutations of the gene have been described not only in the neoplasms usually associated with NF2, but also in 30% of the melanomas and 41 % of the mesotheliomas analyzed. In particular, the finding of mutations in melanomas supports the hypothesis that the NF2 gene is involved in the genesis of several tumor types that arise from the embryonic neural crest. In this study we examined, by single-strand conformational polymorphism (SSCP) analysis, 41 tumors of the central nervous system (11 schwannomas and 30 gliomas), 19 melanomas and 15 Merkel cell carcinoma specimens for mutations in the coding sequence of the NF2 gene. We found three inactivating mutations of the NF2 gene in schwannomas. No alterations of the gene were detected by SSCP analysis of the other tumors. These results confirm the role of NF2 in pathogenesis of schwannomas, but do not define its significance in the genesis of the other neuroectodermal tumors studied.

In plain English

This laboratory study searched tumor samples for mutations in the neurofibromatosis type 2 (NF2) gene. The authors tested 41 central nervous system tumors from 41 unrelated patients (11 schwannomas, 19 diffuse astrocytomas, 6 oligodendrogliomas and 5 ependymomas), 15 Merkel cell carcinoma specimens from 10 patients, and 19 primary skin melanomas grown as cell cultures. They used a screening method called SSCP, followed by DNA sequencing. Mutations were found in 3 of the 11 schwannomas, and none of them was germinal (inherited). Two created a stop codon and one was a frameshift. No mutations were detected in the other tumors. The authors concluded that the study reiterated the importance of the NF2 gene in schwannoma. They judged the gene probably not involved in astrocytic tumors and probably not critical for Merkel cell carcinoma. They said its role in ependymomas and melanomas awaited clarification. They noted that only a small number of ependymomas were examined, all of them intracranial, and that only primary melanomas were analyzed. The study did not examine asbestos. Mesothelioma appears only in the authors' description of earlier work by others.

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: Laboratory genetic analysis of tumor specimens: screening of the NF2 gene coding sequence for mutations by single-strand conformational polymorphism (SSCP) analysis and DNA sequencing
• Who was studied: Surgical specimens from 41 unrelated patients with central nervous system tumors (11 schwannomas, 19 diffuse astrocytomas, 6 oligodendrogliomas, 5 ependymomas); 15 specimens (5 primary tumors, 10 lymph node metastases) from 10 patients with Merkel cell carcinoma; and 19 primary skin melanomas studied as primary cell cultures. Authors were based in Florence, Rome and Milan, Italy; collection dates not given.
• Exposure: No asbestos or other environmental exposure was studied; the study examined NF2 gene mutations in tumor tissue.
• Main results:
  • Mutations were found in 3 of the 11 schwannomas, in exons 6, 11 and 12; none was germinal (inherited).
  • Two schwannoma mutations (cases T330 and T459) created stop codons.
  • The third schwannoma mutation (case T495) was a frameshift.
  • No abnormalities were detected in the other central nervous system tumors, the melanomas or the Merkel cell carcinomas.
  • None of the 15 Merkel cell carcinoma samples (from 10 patients) had detectable NF2 alterations. The authors suggested the gene is probably not critical for this tumor.
  • The authors considered NF2 involvement in astrocytic tumors quite unlikely, citing the absence of alterations in 49 astrocytomas from this study and an earlier study combined.
• The authors' conclusion: The authors concluded that the study reiterates the importance of the NF2 gene in schwannoma and reconfirms that it is probably not involved in astrocytic tumors. They considered a significant role in Merkel tumors unlikely, and said its importance in ependymomas and melanomas awaits further clarification.
• Limitations the authors state:
  • The lack of mutations in ependymomas may reflect the small number examined.
  • Only intracranial ependymomas were studied.
  • Only primary melanomas were analyzed, whereas an earlier study that found mutations mostly examined melanoma metastases.
  • Melanomas were studied as cultured cells, and discrepancies between primary tumors and derived cell lines have been described. The authors considered this an unlikely explanation for all their samples.

Topics

Medical terms in this study, explained in our Lexicon: Bilateral, Neoplasm, Mesothelioma, Carcinoma.

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