NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas

Pe, Leone; Mj, Bello; Jm, De Campos; Vaquero, Jesús; Jl, Sarasa; Pestaña, Ángel; Ja, Rey

doi:10.1038/sj.onc.1202531

Cited by 143 publications

(95 citation statements)

References 41 publications

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“…LOH on 22q, where NF2 is located, is also diffuse in grade I meningiomas and does not appear to be linked to greater malignancy [25][26][27]. Our observations corroborate these findings.…”

Section: Discussionsupporting

confidence: 82%

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

Menghi¹,

Orzan²,

Eoli³

et al. 2011

The Oncologist

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Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down-and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ⌬Ct values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.

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“…LOH on 22q, where NF2 is located, is also diffuse in grade I meningiomas and does not appear to be linked to greater malignancy [25][26][27]. Our observations corroborate these findings.…”

Section: Discussionsupporting

confidence: 82%

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

Menghi¹,

Orzan²,

Eoli³

et al. 2011

The Oncologist

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“…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%

“…However, a careful analysis of the literature shows the existence of disturbing levels of variability as regards the exact incidence of specific genetic abnormalities in meningiomas. As an example, the incidence of monosomy 22/22q -and monosomy 14/14q -ranges between 31% and 78% (14,28 -31) and between 12% and 27% (23,26) of the cases depending on the series analyzed. Although such a variability could be related partially to the small number of cases analyzed in many studies, it might also be due to the use of different methods for the detection of specific genetic abnormalities.…”

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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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“…The most common genetic event associated with meningioma tumorigenesis is chromosome 22q loss of heterozygosity (LOH) with the inactivation of the NF2 gene (Ruttledge et al, 1994;Gutmann et al, 1997;Huynh et al, 1997;Leone et al, 1999;Ueki et al, 1999). Based on structural homology, the NF2 gene product, merlin, belongs to the Protein 4.1 family.…”

Section: Introductionmentioning

confidence: 99%

Disruption of 14-3-3 binding does not impair Protein 4.1B growth suppression

2004

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NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas

Cited by 143 publications

References 41 publications

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

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

Disruption of 14-3-3 binding does not impair Protein 4.1B growth suppression

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