Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2

Wessels, Peter H; Twijnstra, A.; Kessels, Alfons G.H.; Krijne-Kubat, B.; Theunissen, P. H. M. H.; Ummelen, Monique; Ramaekers, Frans C. S.; Hopman, Anton H. N.

doi:10.1002/gcc.10029

Cited by 40 publications

(25 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, large genomic gains of chromosome 7q involving the BRAF locus were present in 38% of cases. This is in line with other studies reporting trisomy of chromosome 7 as a common genomic aberration in adult low-grade astrocytomas (40,41). The impact of BRAF duplications in the pathogenesis of astrocytomas in adults and the relationship between BRAF alteration and other genetic changes in diffuse astrocytomas, e.g., TP53 mutations, remains to be determined.…”

Section: Figuresupporting

confidence: 90%

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

et al. 2008

View full text Add to dashboard Cite

The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication. Furthermore, denaturing HPLC showed that activating BRAF mutations were detected in some of the tumors without BRAF duplication. Similarly, a marked proportion of low-grade astrocytomas from adult patients also had BRAF duplication. Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAF, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas. Our findings implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment.

show abstract

Section: Figuresupporting

confidence: 90%

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

et al. 2008

View full text Add to dashboard Cite

show abstract

“…They observed no trisomy 7 in benign ovarian tumors, trisomy 7 in 30% of low-malignant ovarian tumors, and trisomy 7 in 82% of invasive ovarian cancer. Furthermore, trisomy 7 correlates with shorter survival in astrocytoma (Wessels et al, 2002) glioblastoma (LopezGines et al, 2005), and non-Hodkins lymphoma (Juneja et al, 1997). We observed the strongest signal at 7p15-13 by meta-analysis of three neighboring regions and this is remarkably near the EGFR locus at 7p12.…”

Section: Discussionmentioning

confidence: 56%

Gene expression meta‐analysis identifies chromosomal regions involved in ovarian cancer survival

Thomassen

Jochumsen

Mogensen

et al. 2009

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We summarized mutation load in these regions by a combined mutation score that is statistical significantly associated to survival by analysis in the data sets used for identification of the regions. Furthermore, the prognostic value of the combined mutation score was validated in an independent large data set using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways.

show abstract

“…Gains and losses were scored if there were more or, respectively, fewer signals compared to the signals of the control probe and were interpreted as deletion when more than 30% of the nuclei harbored the alteration and as gain when more than 20% of nuclei were affected. Cutoff levels were determined on paraffin sections of normal brain tissue and were applied in accordance with other studies on paraffin sections [33,44,58].…”

Section: Fluorescence In Situ Hybridization (Fish)mentioning

confidence: 99%

Glioblastomas with Oligodendroglial Component – Common Origin of the Different Histological Parts and Genetic Subclassification

Klink

Schlingelhof

Klink

et al. 2010

Analytical Cellular Pathology

View full text Add to dashboard Cite

Abstract.Background: Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data.Methods: The oligodendroglial and the "classic" glioblastoma parts of 13 GBMO were analyzed separately by interphase fluorescence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue.Results: We identified four distinct genetic subtypes in 13 GBMOs: an "astrocytic" subtype (9/13) characterized by +7/−10; an "oligodendroglial" subtype with −1p/−19q (1/13); an "intermediate" subtype showing +7/−1p (1/13), and an "other" subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part.Conclusion: Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients.

show abstract

Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2

Cited by 40 publications

References 25 publications

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

Gene expression meta‐analysis identifies chromosomal regions involved in ovarian cancer survival

Glioblastomas with Oligodendroglial Component – Common Origin of the Different Histological Parts and Genetic Subclassification

Contact Info

Product

Resources

About