Multiplex ligation-dependent probe amplification (MLPA) screening in meningioma.

Laboratorio de Oncogenética Molecular, Unidad de Investigación, Hospital Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain
Cancer Genetics and Cytogenetics (Impact Factor: 1.93). 04/2007; 173(2):170-2. DOI: 10.1016/j.cancergencyto.2006.09.011
Source: PubMed
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the past 5 to 10 years, important advances were made in the understanding of meningioma biology. Progress in molecular genetics probably represents the most important accomplishment in the comprehensive knowledge of meningioma pathogenesis. Several genes could be identified as targets for mutation or inactivation. Additional chromosomal regions were found to be commonly deleted or amplified, suggesting the presence of further tumor suppressor genes or proto-oncogenes, respectively, in these regions. Histopathologically, the most important innovation is represented by the revised WHO classification in the year 2000. Meningioma grading criteria in the new classification scheme are more precise and objective, and should thus improve consistency in predicting tumor recurrence and aggressive behavior. This review focuses mainly on the advances in molecular biology that were achieved in recent years. It summarizes the most important aspects of meningioma classification as the basis to place biological observations into a correlative context, and, further, includes mechanisms of angiogenesis and edema formation as well as the role of hormone receptors in meningiomas.
    Journal of Neuropathology and Experimental Neurology 05/2004; 63(4):275-86. · 4.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent clinical and molecular research has shed new light on the biology of meningiomas--a common but understudied CNS neoplasm. This review will focus on recent advances and their significance for future research and treatment. Meningiomas represent the second most common brain tumor in adults, and while improved diagnostic modalities are available, these tumors remain underreported. Radiosurgery is an effective adjuvant therapy against meningioma; however, no effective chemotherapy exists. In addition to histologic grading and estimates of the extent of resection, biomarkers, such as progesterone receptor, cyclooxygenase 2, S100A5 and ornithine decarboxylase may be useful in predicting tumor recurrence and/or progression potential in patients with meningioma. On the genetic level, cytogenetic losses on chromosomes 1, 7, 10 and 14 and telomerase activation are observed in clinically aggressive meningioma, whereas monosomy 22 is a common early molecular event in tumor formation. Several candidate growth regulatory genes have been identified, including the Neurofibromatosis 2 (NF2), Tumor Suppressor in Lung Cancer-1 (TSLC1), Protein 4.1B, p53/MDM2 and S6-Kinase genes. The roles of these genes in meningioma formation and progression, as well as the clinical implications of these genetic changes, are discussed. The recent insights into the molecular biology and genetics of meningioma provide new avenues for basic science research aimed at understanding the mechanisms underlying meningioma formation and malignant progression. These advances may be useful in improving our ability to predict clinical outcome and developing targeted therapies to improve outcomes in patients with clinically aggressive meningiomas.
    Current Opinion in Neurology 01/2005; 17(6):687-92. · 5.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The DAL-1/41B gene (differentially expressed in adenocarcinoma of the lung), located in the chromosome 18p11.3 region, belongs to the protein family 4.1 (membrane-associated proteins), which includes the product of the NF2 gene (merlin), and the proteins, ezrin, radixin, and moesin. DAL-1/4.1B is normally expressed at high levels in the brain, with lower levels in the kidney, intestine, and testis. DAL-1/4.1B is known to suppress growth in meningiomas and can be lost in about 60% of sporadic meningiomas as an early event in tumorigenesis; it is a critical growth regulator in the pathogenesis of neoplastic transformation. The similarity between the DAL-1/4.1B protein and merlin, with their high levels of expression in the brain and their recurrent loss in meningiomas, and the lack of previous DAL-1/4.1B mutational analysis reports initiated this mutational study of DAL-1/4.1B in a series of 83 meningiomas. We found the following sequence variations; Ala555Thr (G1663A in exon 13) and Thr950Lys (C2849A in exon 19) in two cases each, and one case with a 5pb deletion (del taaaa) in intron 18. A polymorphism in exon 14 (C2112T/Thr704Thr, also known as C2166T) was also identified; the tumoral allelic constitutions were heterozygous C/T in 15, homo- or hemizygous C in 67 and hemizygous T in one tumour. The low mutational frequency in our study discounts sequence variations in DAL-1/4.1B as the main mechanism underlying participation of this gene in the neoplastic transformation of meningiomas, and suggests that other inactivating mechanisms, such as epigenetic changes, may participate in DAL1/4.1B silencing.
    International Journal of Molecular Medicine 11/2005; 16(4):771-4. · 1.88 Impact Factor


Available from
Jun 2, 2014