Loss of heterozygosity on chromosome 10q associated with malignancy and prognosis in astrocytic tumors, and discovery of novel loss regions

Daido, Shigeru; Takao, Soichiro; Tamiya, Takashi; Ono, Yasuhiro; Terada, Kinya; Ito, Sachio; Ouchida, Mamoru; Date, Isao; Ohmoto, Takashi; Shimizu, Kenji

doi:10.3892/or.12.4.789

Cited by 18 publications

(15 citation statements)

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“…Although some authors claim there is no association with survival, 73,74 others state that this aberration is a negative prognostic factor. 75,76 In turn, an association between EGFR overexpression and a better prognosis in older glioblastoma patients has also been reported, 25,26,33,77 in line with our observations. Noteworthy, we did not find an association between tumor cytogenetics and other disease characteristics, such as patient age 76 and tumor localization, among other features.…”

Section: Discussionsupporting

confidence: 90%

“…20 -22 In turn, genomic deletions of chromosomes 9 and 10 at regions that harbor tumor suppressor genes are also typically found in glioblastomas, where they have been associated with the development of the tumor, its progression, and a poor prognosis. [23][24][25][26] Interestingly, monosomy 10 is associated with gain or amplification of the EGFR gene on chromosome 7p11.2, supporting the role of both alterations in gliomagenesis. 27,28 Other genetic abnormalities that can be frequently found in low-grade gliomas 29,30 [eg, combined del(1p)/ del(19q) and TP53 mutation] are less frequently detected in glioblastomas.…”

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confidence: 88%

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Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Crespo

Vital

Nieto

et al. 2011

The Journal of Molecular Diagnostics

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Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas. ( J Mol Diagn 2011, 13: 634 -647;

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 88%

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Crespo

Vital

Nieto

et al. 2011

The Journal of Molecular Diagnostics

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“…Chromosome 10q allelic loss commonly occurs in glioblastoma, with over 80% of glioblastomas exhibiting loss of heterozygosity (LOH) for at least one locus on chromosome 10q [6], a far more common alteration than alterations in any of the three individual oncogenes residing on 10q. For example, PTEN alterations are seen in 30-44% of glioblastomas [17].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, chromosome 10q allelic loss commonly occurs in glioblastoma, with over 80% of glioblastomas exhibiting loss of heterozygosity (LOH) for at least one locus on chromosome 10q [6].…”

Section: Introductionmentioning

confidence: 99%

Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q

et al. 2009

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Introduction Chromosome 10q allelic loss commonly occurs in glioblastoma. Disruption of PTEN, one of three known 10q tumor suppressor genes, affects the immune system by increasing tumor expression of immunosuppressive protein B7-H1 and by increasing tumor release of Th2-inducing cytokines. While the former might impair antitumor cellular immunity, a consideration for immunotherapy, the latter could cause 10q-maintaining tumor patients to experience comparatively higher rates of bacterial infections, a source of morbidity and mortality in glioblastoma patients. Methods We retrospectively reviewed 58 glioblastoma patients whose tumors were designated ''normal-10q'' (n = 16) or ''LOH-10q'' (n = 42) using loss of heterozygosity (LOH) assays of microsatellite markers in constitutional/tumor DNA pairs. Records were reviewed for symptomatic, microbiologically or radiographically confirmed infections in the first 2 years after diagnosis. Results Infection occurred more frequently in ''normal-10q'' than ''LOH-10q'' patients (56% vs. 14% of patients experiencing infection; P = 0.001). ''Normal-10q'' patients more commonly developed all four infection types studied (urinary tract = 38% vs. 13%, craniotomy wound = 19% vs. 0%, pneumonia = 19% vs. 5%, sepsis = 6% vs. 3%). ''Normal10q'' and ''LOH-10q'' patients had similar survival, ages, chemotherapy treatment rates, and frequency of patients on dexamethasone 1 month after radiation therapy (P = 0.4-0.98), making these factors unlikely to explain the observed difference in infection rates. Conclusion While tumor mutations may inhibit antitumor immunity, the effects of these mutations on systemic immunity remain undetermined. We found higher infection rates after glioblastoma diagnosis in patients whose tumors maintained chromosome 10q than in patients whose tumors had allelic 10q loss. Differing effects of this genetic alteration on antitumor and systemic immunity may warrant further investigation, potentially providing insight into mechanisms of antitumor immunity and host defenses against local and systemic infections.

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“…However, some LOH appear to be correlated with OS: 10q26, which carries DMBT 1 (deleted in malignant brain tumours), is a possible tumour suppressor gene in glial tumours (Mollenhauer et al, 1997). It is generally accepted that passage from an anaplastic phenotype to a GBM phenotype is associated with 10q LOH (Fujisawa et al, 1999;Daido et al, 2004), although the role specifically played by DMBT 1 in this progression is controversial (Sasaki et al, 2002). Taken all together, these results suggest firstly that an increased frequency of this LOH is associated with increasing grade.…”

Section: Lohmentioning

confidence: 99%

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study

et al. 2008

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This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan -Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14 ARF , p16 INK4A and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

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Loss of heterozygosity on chromosome 10q associated with malignancy and prognosis in astrocytic tumors, and discovery of novel loss regions

Cited by 18 publications

References 0 publications

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study

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