Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review

Our plain-English summary of Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review, by R.N. Prasad, U.G. Gardner, A. Yaney, et al (Frontiers in Oncology, 2021).

The study

• Authors: R.N. Prasad, U.G. Gardner, A. Yaney, D.M. Prevedello, D.C. Koboldt, D.L. Thomas, E.R. Mardis, J.D. Palmer
• Journal: Frontiers in Oncology
• Published: 2021;11:721712
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Meningioma is the most common primary brain tumor, and recurrence risk increases with increasing WHO Grade from I to III. Rhabdoid meningiomas are a subset of WHO Grade III tumors with rhabdoid cells, a high proliferation index, and other malignant features that follow an aggressive clinical course. Some meningiomas with rhabdoid features either only focally or without other malignant features are classified as lower grade yet still recur early. Recently, inactivating mutations in the tumor suppressor gene BAP1 have been associated with poorer prognosis in rhabdoid meningioma and meningioma with rhabdoid features, and germline mutations have been linked to a hereditary tumor predisposition syndrome (TPDS) predisposing patients primarily to melanoma and mesothelioma. We present the first report of a familial BAP1 inactivating mutation identified after multiple generations of a family presented with meningiomas with rhabdoid features instead of with previously described BAP1 loss-associated malignancies. A 24-year-old female presented with a Grade II meningioma with rhabdoid and papillary features treated with subtotal resection, adjuvant external beam radiation therapy, and salvage gamma knife radiosurgery six years later. Around that time, her mother presented with a meningioma with rhabdoid and papillary features managed with resection and adjuvant radiation therapy. Germline testing was positive for a pathogenic BAP1 mutation in both patients. Sequencing of both tumors demonstrated biallelic BAP1 inactivation via the combination of germline BAP1 mutation and either loss of heterozygosity or somatic mutation. No additional mutations implicated in oncogenesis were noted from either patient's germline or tumor sequencing, suggesting that the inactivation of BAP1 was responsible for pathogenesis. These cases demonstrate the importance of routine BAP1 tumor testing in meningioma with rhabdoid features regardless of grade, germline testing for patients with BAP1 inactivated tumors, and tailored cancer screening in this population.

Copyright © 2021 Prasad, Gardner, Yaney, Prevedello, Koboldt, Thomas, Mardis and Palmer.

In plain English

This article was a case series of two related patients with a literature review. It did not study asbestos. Mesothelioma appeared only as one of the cancers that earlier studies linked to inherited BAP1 mutations. A 24-year-old woman (Patient A) had a WHO grade II meningioma with rhabdoid and papillary features. It was partly removed and treated with radiation, and it recurred over 6 years later. Around that time her 57-year-old mother (Patient B) had a meningioma with rhabdoid and papillary features, also partly removed and treated with radiation. Both women carried the same inherited BAP1 mutation. In each tumor the second copy of BAP1 was also inactivated: by a new mutation in Patient A, and by loss across chromosome 3 in Patient B. No other mutations were found in known cancer genes, apart from one PIK3CA change in Patient B's tumor not previously reported as disease-causing. The authors concluded that genetic testing should be offered to patients with BAP1-inactivated tumors and that routine BAP1 tumor testing may aid prognosis. They noted that follow-up for Patient B was limited.

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 series of two patients (daughter and mother) with a literature review
• Who was studied: Two members of one family treated at The Ohio State University: a 24-year-old woman (Patient A) and her 57-year-old mother (Patient B), both with meningioma with rhabdoid features
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was an inherited (germline) pathogenic BAP1 mutation, c.1777C>T (p.Gln593*).
• Main results:
  • Patient A's tumor had rhabdoid and papillary features but no other malignant features. It was diagnosed as atypical meningioma, WHO grade II.
  • Patient A tested positive for the germline BAP1 mutation, and her mother (Patient B) then tested positive for the same mutation
  • In Patient A's tumor, the second BAP1 copy was inactivated by an 11-base pair frameshift mutation
  • In Patient B's tumor, the second BAP1 copy was lost through loss of heterozygosity across all of chromosome 3
  • Patient A's tumor had 3 additional somatic coding mutations and Patient B's had 18. None was in known cancer genes or meningioma-associated genes, except a missense PIK3CA mutation in Patient B's tumor that had not previously been noted to be pathogenic.
  • Patient A's disease recurred more than 6 years after resection and was treated with gamma knife radiosurgery. At more than 7 years post-resection she had no evidence of new recurrence or progression.
  • Patient B had no clinical or radiographic evidence of disease nine months after resection
  • Family history included kidney cancer at age 52 in Patient B's sister and lung cancer in Patient B's father
• The authors' conclusion: The authors concluded that routine tumor testing for BAP1 inactivation may aid prognosis in lower-grade tumors with rhabdoid features. They also concluded that genetic testing should be offered to patients with BAP1-inactivated tumors, and that surveillance for ocular and cutaneous melanoma should be considered for carriers.
• Limitations the authors state:
  • Follow-up for Patient B was relatively limited
  • Germline genetic testing for asymptomatic family members was not available
  • Surgical pathology from family members who had died of cancer was not available for tumor sequencing

Topics

Medical terms in this study, explained in our Lexicon: BAP1 Tumor Predisposition Syndrome, Rhabdoid, Tumor Suppressor Gene, BAP1, Prognosis, Germline Mutation, Mesothelioma, Somatic Mutation.

Related studies

• Giant Pediatric Rhabdoid Meningioma Associated with a Germline BAP1 Pathogenic Variation: A Rare Clinical Case — A.C. Ravanpay, A. Barkley, et al. (2018)
• Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature — D. Hassan, S. Ligato (2019)
• Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation — C. Ribeiro, S. Campelos, et al. (2013)
• Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members — M. Kittaneh, C. Berkelhammer (2018)
• CT features of primary pleural gritty meningioma: A case report and review of the literature — X. Qin, C. Zeng, et al. (2023)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)

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