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|Year : 2016 | Volume
| Issue : 6 | Page : 1264-1265
Genomic characterization of meningiomas: Fluorescence In-situ hybridization analysis for chromosome 14q deletion in subsets of meningiomas in a cohort of Indian patients
Vernon Velho, Harish Naik
Department of Neurosurgery, J J Hospital and Grant Medical College, Mumbai, Maharashtra, India
|Date of Web Publication||11-Nov-2016|
Department of Neurosurgery, J J Hospital and Grant Medical College, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Velho V, Naik H. Genomic characterization of meningiomas: Fluorescence In-situ hybridization analysis for chromosome 14q deletion in subsets of meningiomas in a cohort of Indian patients. Neurol India 2016;64:1264-5
|How to cite this URL:|
Velho V, Naik H. Genomic characterization of meningiomas: Fluorescence In-situ hybridization analysis for chromosome 14q deletion in subsets of meningiomas in a cohort of Indian patients. Neurol India [serial online] 2016 [cited 2019 Jul 20];64:1264-5. Available from: http://www.neurologyindia.com/text.asp?2016/64/6/1264/193761
After reading the article, “Fluorescence in situ hybridization for chromosome 14q deletion in subsets of meningioma segregated by MIB-labelling index,” we wish to present our thoughts and insights on this subject.
Although few studies are available in the Western literature on molecular alteration in meningiomas, not much data has been reported regarding genetic alterations in these tumors from India and Asian countries. A single study by Asirvatham et al., found that loss of heterozygosity 14q was more frequent in meningiomas of high grade compared to that of benign meningiomas.
Genomic characterization of meningiomas could be an efficient route to improve the understanding of meningioma tumorigenesis, which is a necessary step in the design of new and rational therapeutic agents., Studies on genetic alterations in meningiomas have lagged compared to those of other central nervous system (CNS) neoplasms. Most molecular alterations are poorly characterized and the genetic classification of meningiomas is still in its infancy.
In recent years, cytogenetic fluorescence in-situ hybridization (FISH), comparative genomic hybridization (CGH), and array CGH methods have allowed various investigators to report deletions of a number of loci in different grades of meningiomas. The most common chromosomal aberration is the monosomic loss of chromosome 22, which occurs in a majority of these tumors. In particular, the loss of 1p has been suggested as a decisive step for meningioma progression. Loss of 14q is another frequently detected abnormality, which has been found to be associated with high grades of meningiomas and a worse prognosis. In this article, 46 specimens of meningiomas were segregated into 5 categories based on the MIB labelling index (LI) of <5%, 5–7.5%, 7.5–9.9%, 10%, and >10%; however, no standard method of randomization was used to select the cases out of 166 tumor samples. It would have been appropriate if the author had mentioned the basis or any reference for such segregation. Was the sample selected from tumor tissues of recurrent meningiomas because recurrent cases of meningiomas have a high incidence of allelic loss of 14q? FISH probes targeted which region of chromosome 14q, because as per the literature, 14q13 and 14q32 are the more common regions involved? There is no mention in the study regarding 1p/14q codeletion as it is more commonly seen in high grades of meningiomas. Chromosome 1p36 deletion is an early event in the pathogenesis of meningiomas, the frequency of which increases with an increase in the tumor grade. Isolated 14q deletion is extremely rare. This molecular alteration gets added on to 1p36 deletion as the tumor grade increases.
The study does not mention the location and type of surgical resection (gross total resection versus subtotal resection) of meningiomas as it affects the incidence of recurrence; and, if the cases included were those of either recurrent or residual lesion? Although meningiomas at different sites display similar histopathological features, there is considerable variability in the clinical outcome of tumors arising in different locations. The location of these tumors influences the extent of resection, which in turn has an impact on the development of recurrence. While convexity tumors are easily accessible and well-circumscribed, skull base meningiomas, particularly petroclival tumors, are more invasive and are often intimately associated with critical neurovascular structures, thus presenting a unique therapeutic challenge that may preclude complete resection. Understanding the molecular biology of these invasive meningiomas enveloping sensitive neurovascular structures, in which gross total resection is not safely feasible without morbidity, may provide an insight into factors influencing recurrence in petroclival meningiomas as well as provide targets for the development of novel therapeutic agents. The article has not mentioned the follow-up period and whether any adjuvant treatment was given for tumors with 14q deletion. As suggested by Devaprasath et al., tumors that did not show any histologic features of atypia but had a high MIB-LI must be followed-up closely. The reference given by the article number 25 does not mention the percentage of 14q deletion in each grade.
The role of chromosome 14q in the tumorigenesis of meningiomas occurring in the Indian population has been further investigated and well-assessed in this article. Molecular assessment for 14q status may provide prognostically useful information beyond that obtained by routine histopathology. However, a number of complex clinical questions remain: (1) Which meningiomas should be examined by FISH for 14q deletion? (2) Should all meningiomas be examined or only the benign samples? (3) Should all the benign meningiomas be examined or only those with gross total resection because this is the subset not normally expected to recur? (4) How should the finding of 14q loss in an otherwise benign meningioma affect patient management? (5) Would this simply warrant more careful radiographic follow-up or would adjuvant therapy be necessary for achieving an improved local control? Prospective randomized studies and incorporation of such genetic data into future therapeutic trials will be necessary to answer some of these remaining questions.
To summarize, we support the hypothesis that 1p and 14q deletions are common events in the malignant progression of meningiomas, the frequency of which increases with increase in tumor grade. In some cases, 14q deletions precede histologic evidence of aggressiveness. Nonetheless, such benign-appearing cases seem more likely to recur even after gross total resection. Therefore, in selected cases, FISH assessment of 14q status may be of diagnostic value. Likewise, combined 1p and 14q deletions are particularly associated with a more malignant phenotype, and this may have diagnostic value in borderline atypical meningiomas. Petroclival tumors harboring the 1p/14q co-deletion, a genetic marker for aggressive behavior, should be treated with caution, as they may behave more aggressively than those without co-deletion. This is particularly important for incompletely resected tumors, in which 1p/14q co-deletion can be used as a marker for prognostication and prediction of recurrence.
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