Paired Primary and Recurrent Rhabdoid Meningiomas: Cytogenetic Alterations, BAP1 Gene Expression Profile and Patient Outcome

TL;DR

This study compares genetic and clinical features of recurrent and non-recurrent rhabdoid meningiomas, finding distinct chromosomal patterns and BAP1 expression differences that may influence patient outcomes.

Contribution

The paper identifies specific cytogenetic alterations and BAP1 expression profiles in recurrent rhabdoid meningiomas that distinguish them from non-recurrent cases.

Findings

Recurrent rhabdoid meningiomas show higher genetic instability and chromosomal losses at 1p, 14q, 18, and 22 at diagnosis.

Non-recurrent tumors more frequently exhibit losses at 19p/q and gains at 20 and 21.

BAP1 loss increases from one-third at diagnosis to 100% in recurrences, and 17q22 gains are linked to deceased patients.

Abstract

Rhabdoid meningiomas are a rare subtype of (per definition) grade 3 meningiomas of unknown cause, with a heterogeneous clinical course and higher recurrence rates, even among tumors undergoing complete surgical removal, for whom early postoperative radiotherapy may favor local control of the disease and prolonged survival. Here, we compared the clinical, biological and genetic features (at diagnosis and in sequential tumor recurrences) of recurrent vs. non-recurrent rhabdoid meningiomas in a retrospective series of 15 patients with a long follow-up. Recurrent RM showed a higher genetic instability at diagnosis associated with multiple chromosomal losses involving chromosomes 1p, 14q, 18 and 22. Non-recurrent RM were genetically less complex tumors which more frequently showed extensive losses at chromosome 19p and/or 19q, together with gains of chromosomes 20 and 21. Comparison of paired primary vs. recurrent tumor samples of recurrent RM revealed additional losses of chromosomes 16q and 19p, together with gains of chromosomes 1q and 17q. Of note, focal chromosome gains at 17q22 were exclusively found in women with recurrent RM who died, although survival differences did not reach statistical significance.

Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients.

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