Allelic Losses in Neurofibromatosis 2-Associated Meningiomas

Lamszus, Katrin; Vahldiek, Felix; Mautner, Victor‐Felix; Schichor, Christian; Tonn, Jörg C.; Stavrou, D.; Fillbrandt, Regina; Westphal, Manfred; Kluwe, Lan

doi:10.1093/jnen/59.6.504

Cited by 46 publications

(27 citation statements)

References 32 publications

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“…Of note, this sample is the only one in the NF2-nonmutated group that harbors 22q loss; thus, this sample might indeed have NF2 inactivation through, for example, epigenetic mechanisms. In the literature, the NF2 status of meningioma samples is seldom determined, but review of literature clustering samples according to their 22q status also finds an association between 22q loss and FAL in the meningiomas studied (14,35,36,(46)(47)(48). These studies are in agreement with our finding that NF2 inactivation in meningiomas is associated with greater chromosome instability.…”

Section: Nf2 Loss Is Associated With Chromosome Instability In Progresupporting

confidence: 89%

Genomic Profiling Reveals Alternative Genetic Pathways of Meningioma Malignant Progression Dependent on the UnderlyingNF2Status

Goutagny

Yang

Zucman‐Rossi

et al. 2010

Clinical Cancer Research

107

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Purpose: Meningiomas are the most common central nervous system tumors in the population of age 35 and older. WHO defines three grades predictive of the risk of recurrence. Clinical data supporting histologic malignant progression of meningiomas are sparse and underlying molecular mechanisms are not clearly depicted.Experimental Design: We identified genetic alterations associated with histologic progression of 36 paired meningioma samples in 18 patients using 500K SNP genotyping arrays and NF2 gene sequencing.Results: The most frequent chromosome alterations observed in progressing meningioma samples are early alterations (i.e., present both in lower-and higher-grade samples of a single patient). In our series, NF2 gene inactivation was an early and frequent event in progressing meningioma samples (73%). Chromosome alterations acquired during progression from grade I to grade II meningioma were not recurrent. Progression to grade III was characterized by recurrent genomic alterations, the most frequent being CDKN2A/CDKN2B locus loss on 9p.Conclusion: Meningiomas displayed different patterns of genetic alterations during progression according to their NF2 status: NF2-mutated meningiomas showed higher chromosome instability during progression than NF2-nonmutated meningiomas, which had very few imbalanced chromosome segments. This pattern of alterations could thus be used as markers in clinical practice to identify tumors prone to progress among grade I meningiomas. Clin Cancer Res; 16(16); 4155-64. ©2010 AACR.

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Section: Nf2 Loss Is Associated With Chromosome Instability In Progresupporting

confidence: 89%

Genomic Profiling Reveals Alternative Genetic Pathways of Meningioma Malignant Progression Dependent on the UnderlyingNF2Status

Goutagny

Yang

Zucman‐Rossi

et al. 2010

Clinical Cancer Research

107

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“…Previous studies in sporadic meningiomas show a high frequency (44 -100%) of LOH on chromosome 22q12 at NF2 gene locus (35, 39 -44), and patients with NF2 develop menigiomas that have a high frequency of NF2 gene LOH (49). Our results from allelotyping of 22q12 in the MEN 1-associated meningioma show that there is no LOH on chromosome 22q12 in the region of the NF2 gene.…”

Section: Discussionsupporting

confidence: 45%

“…Previous studies have shown a high frequency of LOH on chromosome 1p LOH (28 -57%) and at 22q12 (44 -100%) at the NF2 tumor suppressor gene locus (28, 35, 39 -48) in sporadic meningiomas and in NF2-associated meningiomas (49), and their presence correlates with an aggressive growth pattern, tumor site, high histological grade, and decreased recurrencefree survival (40, 41, 44 -46). To assess these genetic alterations (NF2 and 1p) as well as possible LOH at the MEN1 locus on chromosome 11q13 in this MEN 1-associated meningioma, each of these regions was examined with polymorphic microsatellite markers (Figs.…”

Section: Resultsmentioning

confidence: 99%

Meningiomas May Be a Component Tumor of Multiple Endocrine Neoplasia Type 1

Asgharian

Chen

Patronas³

et al. 2004

Clinical Cancer Research

111

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Purpose: Recently, an increased incidence of some nonendocrine tumors are reported in patients with multiple endocrine neoplasia type 1 (MEN 1). There are rare reports of meningiomas and other central nervous system tumors in these patients, but it is unknown if they are more frequent or if allelic loss of the MEN1 gene is important in their pathogenesis. The aim of this study was to address these two latter questions.Experimental Design: Results from a prospective study of 74 MEN 1 patients with suspected/proven pancreatic endocrine tumors (PETs) were analyzed, as well as molecular studies performed on a resected meningioma. All patients had serial brain imaging studies (computed tomography, magnetic resonance imaging, and octreoscanning since 1994) and yearly studies evaluating MEN 1 involvement with a mean follow-up of 7.2 years. Results were compared with 185 patients with sporadic Zollinger-Ellison syndrome.Results: Six patients (8%) had meningiomas. Meningiomas were single and found late in the MEN 1 course (mean age ‫؍‬ 51 years). Magnetic resonance imaging/computed tomography were more sensitive than octreoscanning. Their diagnosis averaged 18 years after the onset of hyperparathyroidism, 10 -15 years after pituitary disease or PETs. Meningiomas were 11 times more frequent in patients with PETs with MEN 1 than without MEN 1 (P ‫؍‬ 0.017). No clinical, laboratory, or MEN 1 feature distinguished patients with meningiomas. Meningiomas were asymptomatic and 60% showed no growth. A resected meningioma showed loss of heterozygosity at 11q13 and 1p, including at p73 and ARHI/NOEY2 locus, but not at the neurofibromatosis 2 gene locus.Conclusions: These results show meningiomas are not an infrequent occurrence in MEN 1, and loss of the function of the MEN1 gene product plays a role in their pathogenesis in these patients.

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“…Loss of a sex Table 2 Correlation Between the Numerical Abnormalities Observed for Chromosomes 1,9,10,11,14,15,17,22 chromosome in somatic cells is a relatively frequent agerelated phenomenon, usually including loss of the Y chromosome in bone marrow cells from older male individuals (40). However, it was never found at the high frequencies reported here.…”

Section: Discussionmentioning

confidence: 99%

“…From the reported individual abnormalities, the monosomy 22/22q -deletion is, by far, the most frequent aberration detected in typical meningiomas (2,7,12,14,17,19 -21). Other chromosome abnormalities described as relatively frequent in these tumors include loss/deletion of chromosomes 1p, 14q, 10q, and the sexual chromosomes (22)(23)(24)(25)(26)(27). In contrast, chromosome gains and complex karyotypes are usu-ally found in a low proportion of cases.…”

mentioning

confidence: 99%

Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome‐specific probes

et al. 2002

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Objective: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity. Methods: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied. Results: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q -deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q -was associated with monosomy X in females and monosomy 14/14q -was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells. Conclusions: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH. Cytometry (Clin. Cytometry) 50:153-159, 2002.

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Allelic Losses in Neurofibromatosis 2-Associated Meningiomas

Cited by 46 publications

References 32 publications

Genomic Profiling Reveals Alternative Genetic Pathways of Meningioma Malignant Progression Dependent on the UnderlyingNF2Status

Genomic Profiling Reveals Alternative Genetic Pathways of Meningioma Malignant Progression Dependent on the UnderlyingNF2Status

Meningiomas May Be a Component Tumor of Multiple Endocrine Neoplasia Type 1

Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome‐specific probes

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