Loss of Heterozygosity 1p36 and 19q13 Is a Prognostic Factor for Overall Survival in Patients With Diffuse WHO Grade 2 Gliomas Treated Without Chemotherapy

Mariani, Luigi; Deiana, Gianluca; Vassella, Erik; Fathi, Ali-Reza; Murtin, Christine; Arnold, Marlène; Vajtai, István; Weis, Joachim; Siegenthaler, P; Schobesberger, Martina; Reinert, Michael

doi:10.1200/jco.2006.05.9238

Cited by 79 publications

(56 citation statements)

References 24 publications

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“…DNA methylation patterns in the CpG island of the MGMT gene was determined by the method of methylation-specific PCR as previously described (10,11). Genotypes for multiple loci for loss of heterozygosity analysis were determined by PCR using fluorescent primers tagged with FAM (Hokkaido system science) for microsatellite markers on chromosome 1p36 and 19q13 as previously described (12,13). P53 mutation status was analyzed by sequencing between exons 4 and 10, including the DNA-binding domain as previously described (14).…”

Section: Methodsmentioning

confidence: 99%

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

Shirahata

Iwao-Koizumi

Saitō

et al. 2007

Clinical Cancer Research

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Purpose: Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. Experimental Design: The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Results: Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Conclusions: Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

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Section: Methodsmentioning

confidence: 99%

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

Shirahata

Iwao-Koizumi

Saitō

et al. 2007

Clinical Cancer Research

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“…Both deletions of 1p/19q frequently occur together and are seldom found as a separate alteration [4,19,24]. It is estimated that frequency of concurrent 1p and 19q deletion approaches 70-80% in oligodendrogliomas, 30-50% in mixed gliomas and only 7-15% in astrocytomas [4,19,24]. The deletion of 1p/19q is referred to as the most common genetic abnormality observed in oligodendrogliomas.…”

Section: Introductionmentioning

confidence: 99%

“…Although chromosome 19q deletion used to be regarded a feature of both oligodendrogliomas and astrocytomas, further studies have shown its predominance in the former group [28]. Both deletions of 1p/19q frequently occur together and are seldom found as a separate alteration [4,19,24]. It is estimated that frequency of concurrent 1p and 19q deletion approaches 70-80% in oligodendrogliomas, 30-50% in mixed gliomas and only 7-15% in astrocytomas [4,19,24].…”

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confidence: 99%

Original article Loss of genetic material within 1p and 19q chromosomal arms in low grade gliomas of central nervous system

Ręcławowicz

Stempniewicz²,

Biernat³

et al. 2013

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Loss of genetic material within 1p and 19q chromosomal arms in low grade gliomas of central nervous system D Da an ni ie el l R Rę ęc cł ła aw wo ow wi ic cz z 1 1 , , M Mi ir ro os sł ła aw w S St te em mp pn ni ie ew wi ic cz z 1 1 , , W Wo oj jc ci ie ec ch h B Bi ie er rn na at t 2 2 , , J Ja an nu us sz z L Li im mo on n 3 3 , , P Pa aw we eł ł S Sł ło on ni ie ew ws sk ki i IntroductionThe definition of low grade glioma encompasses three types of WHO grade II tumours including: diffuse astrocytoma (DA), oligodendroglioma (OD), and mixed glioma -oligoastrocytoma (OA). They constitute up to 30% of all glial tumours of the central nervous system. Distinguishing between these three types may be challenging due to both subjectivity of pathologists' judgment and lack of reliable objective markers confirming the diagnosis. The WHO classification does not pro vide the exact cut-off values of the oligodendroglial Folia Neuropathologica 2013; 51/1 27 and astrocytic component between three aforementioned types of tumours. Thus, discrepancy among pathologists exists, some use a 50% threshold level for the oligodendroglial component in making the diagnosis of oligodendroglioma [31], whereas others use a 10% cut-off [15].Recent publications suggest that deletion of chromosomal arm 1p/19q may play such an indicative role in the diagnosis of low grade gliomas (LGG) [1,11].LGGs demonstrate a broad range of genetic disturbances. One of the frequent alterations is simultaneous deletion of the short arm of chromosome 1 and the long arm of chromosome 19 [9]. Although chromosome 19q deletion used to be regarded a feature of both oligodendrogliomas and astrocytomas, further studies have shown its predominance in the former group [28]. Both deletions of 1p/19q frequently occur together and are seldom found as a separate alteration [4,19,24]. It is estimated that frequency of concurrent 1p and 19q deletion approaches 70-80% in oligodendrogliomas, 30-50% in mixed gliomas and only 7-15% in astrocytomas [4,19,24]. The deletion of 1p/19q is referred to as the most common genetic abnormality observed in oligodendrogliomas. Therefore, 1p/19q deletion seems to be a reliable signature of this neoplasm.In addition, the deletion of 1p/19q is additionally a predictive factor in OD. Cairncross et al. demonstrated that 1p deletion is a marker of the tumour che mosensitivity to procarbazine, lomustine and vincristine scheme (PCV) and concurrent 1p/19q deletion is a positive factor for a longer time to progression in anaplastic oligodendrogliomas [7]. Additionally, the use of multivariate statistics showed that survival in patients with 1p/19q loss is statistically longer than in patients without this alteration. These results were confirmed by retrospective analyses based on clinical studies EORTC 26951 and RTOG 9402. Both proved that presence of co-deletion correlates with the extended time to progression and time do death in grade III [3,6] and grade II gliomas [12]. Moreover, the latter study disclosed beneficial response to chemotherapy in...

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“…In particular, the concomitant presence of LOH in 1p and 19q chromosome arms or in 1p alone has been proposed as a potential indicator of responsiveness to chemotherapy and of prolonged survival in anaplastic oligodendroglioma patients (4,11,12). Although the same alterations have also been reported to be correlated with prolonged overall survival in grade II oligodendrogliomas (ODG II) (13)(14)(15), this was not confirmed in a recent study based on multiplex ligationdependent probe amplification analysis (16).…”

Section: Introductionmentioning

confidence: 54%

Chromosome 1p and 19q evaluation in low-grade oligodendrogliomas: A descriptive study

Calistri¹

2009

Int J Mol Med

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Abstract. Oligodendrogliomas are rare primary brain tumors with variable patient outcomes which are not always adequately accounted for by clinical or pathological variables. The present study evaluated the prognostic implications of chromosome 1p and 19q status in a set of 23 low grade oligodendrogliomas (OGD II), and correlated the results with patient outcome. Loss of heterozygosity (LOH) and fluorescent in situ hybridization (FISH) analyses, the most widely used standard procedures, were used. 1p and 19q deletions were found in 65 and 61% of cases, respectively, using FISH and in 78 and 72% of cases using LOH. Both deletions were found in 56 and 64% of patients using FISH and LOH, respectively. Concordance between the results from the two techniques, determined by the Kappa statistics, ranged from fair to substantial depending on whether single or combined deletions were considered. Our results showed that the molecular alterations are associated with age and tumor localization. With regard to the impact of chromosomal alterations on clinical outcome, chromosome 19q deletions detected by LOH would seem to indicate a subgroup of patients at a higher risk of relapse, although the small number of patients recruited does not permit any definitive conclusions to be drawn. Further studies are now ongoing to determine whether this methodological approach could be potentially useful in low grade oligodendrogliomas to better characterize chromosomal alterations of 1p/19q and identify subgroups of patients with a higher risk of disease recurrence.

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Loss of Heterozygosity 1p36 and 19q13 Is a Prognostic Factor for Overall Survival in Patients With Diffuse WHO Grade 2 Gliomas Treated Without Chemotherapy

Abstract: The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.

Cited by 79 publications

References 24 publications

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

Original article Loss of genetic material within 1p and 19q chromosomal arms in low grade gliomas of central nervous system

Chromosome 1p and 19q evaluation in low-grade oligodendrogliomas: A descriptive study

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