Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic neurofibromas

Kinoshita, Toshihiko; Iwasaki, Hiroshi; Ishiguro, Masako; Matsuzaki, Akio; Kikuchi, Masahiro

doi:10.1016/s0165-4608(02)00527-7

Cited by 33 publications

(28 citation statements)

References 33 publications

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“…Deletions were more frequent than amplifications in MPNSTs, which is in agreement with the earlier CGH studies (15,27). Moreover, this microarray study substantiates our previous observation that it is the loss of NF1 gene, as evidenced by loss of heterozygosity that is a common somatic mutation in MPNSTs but is not a predominant germline mutation (28).…”

Section: Deleted Genessupporting

confidence: 92%

“…Although previous investigations in MPNSTs have presented aberrations from 5q33, 11q22, and 17q25 (16,17,27), harboring HMMR, MMP13, and ITGB4 genes, respectively, this study reports the involvement of specific genes from these loci. Hemizygous deletion of the HMMR/RHAMM gene, coding for Rhamm (a hyaluronan binding protein), was observed in 46% of the MPNSTs.…”

Section: Deleted Genesmentioning

confidence: 57%

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High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization

Mantripragada

Spurlock

Kluwe

et al. 2008

Clinical Cancer Research

117

111

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Purpose: Neurofibromatosis type1 (NF1) is an autosomal dominant condition that predisposes to benign and malignant tumors. The lifetime risk of a malignant peripheral nerve sheath tumor (MPNST) in NF1is f10%.These tumors have a poor survival rate and their molecular basis remains unclear.We report the first comprehensive investigation of DNA copy number across multitude of genes in NF1tumors using high-resolution array comparative genomic hybridization (CGH), with the aim to identify molecular signatures that delineate malignant from benign NF1tumors. Experimental Design: We constructed an exon-level resolution microarray encompassing 57 selected genes and profiled DNA from 35 MPNSTs, 16 plexiform, and 8 dermal neurofibromas. Bioinformatic analysis was done on array CGH data to identify concurrent aberrations in malignant tumors. Results: The array CGH profiles of MPNSTs and neurofibromas were markedly different. A number of MPNST-specific alterations were identified, including amplifications of ITGB4, PDGFRA, MET, TP73, and HGF plus deletions in NF1, HMMR/RHAMM, MMP13, L1CAM2, p16INK4A/ CDKN2A, andTP53. Copy number changes of HMMR/RHAMM, MMP13, p16INK4A/CDKN2A, and ITGB4 were observed in 46%, 43%, 39%, and 32%, respectively of the malignant tumors, implicating these genes in MPNST pathogenesis. Concomitant amplifications of HGF, MET, and PDGFRA genes were also revealed in MPNSTs, suggesting the putative role of p70S6K pathway in NF1tumor progression. Conclusions: This study highlights the potential of array CGH in identifying novel diagnostic markers for MPNSTs.Neurofibromatosis type 1 (NF1; OMIM # 162200) is a common autosomal dominant disorder with a prevalence of 1 in 3,000 individuals worldwide. The majority of individuals with NF1 develop benign dermal neurofibromas, and approximately one third have benign plexiform neurofibromas (1, 2). In 5% to 10% of NF1 patients, neurofibromas (predominantly plexiform) develop into malignant peripheral nerve sheath tumors (MPNST; ref. 3). Whereas approximately half of all MPNSTs in the general population occur in the context of NF1, the other 50% are sporadic in origin. To date, understanding of histogenesis and the molecular mechanisms leading to the malignancy in NF1 remains fragmentary.

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Section: Deleted Genessupporting

confidence: 92%

Section: Deleted Genesmentioning

confidence: 57%

High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization

Mantripragada

Spurlock

Kluwe

et al. 2008

Clinical Cancer Research

117

111

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“…These findings were recapitulated in another publication by this group, 129 in which 12 NF1-associated tumors and 12 sporadic cases were analyzed using CGH. In this study, chromosomal imbalances were more common in NF1-associated tumors than in sporadic neurofibromas, with both groups showing predominantly more losses than gains, and it revealed novel chromosomal imbalances including chromosomes 17, 19, and chromosome arm 22q, which may be related to oncogenes or tumor suppressor genes in neurofibromas.…”

Section: Tumors Of Cranial and Spinal Nervessupporting

confidence: 58%

Molecular cytogenetic analysis in the study of brain tumors: findings and applications

Bayani¹,

Pandita²,

Squire³

2005

FOC

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Classic cytogenetics has evolved from black and white to technicolor images of chromosomes as a result of advances in fluorescence in situ hybridization (FISH) techniques, and is now called molecular cytogenetics. Improvements in the quality and diversity of probes suitable for FISH, coupled with advances in computerized image analysis, now permit the genome or tissue of interest to be analyzed in detail on a glass slide. It is evident that the growing list of options for cytogenetic analysis has improved the understanding of chromosomal changes in disease initiation, progression, and response to treatment. The contributions of classic and molecular cytogenetics to the study of brain tumors have provided scientists and clinicians alike with new avenues for investigation. In this review the authors summarize the contributions of molecular cytogenetics to the study of brain tumors, encompassing the findings of classic cytogenetics, interphase- and metaphase-based FISH studies, spectral karyotyping, and metaphase- and array-based comparative genomic hybridization. In addition, this review also details the role of molecular cytogenetic techniques in other aspects of understanding the pathogenesis of brain tumors, including xenograft, cancer stem cell, and telomere length studies.

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“…The AGS1/RASD1 gene maps to human chromosome 17p11.2, a region associated with a high incidence of loss of heterozygosity and deletions in cancers (Soenen et al, 1998;Stacey et al, 1999;Koga et al, 2002). The current studies indicate that a component of aberrant cell growth in certain tissues may reflect a loss of the control mechanisms that maintain AGS1/RASD1 expression.…”

Section: Resultsmentioning

confidence: 62%

The Ras-related protein AGS1/RASD1 suppresses cell growth

et al. 2004

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AGS1/RASD1 is a Ras-related protein identified as a dexamethasone-inducible cDNA and as a signal regulator in various functional and protein-interaction screens. As an initial approach to define the role of AGS1/RASD1 as a Ras-family member, we determined its influence on cell growth/survival. In clonogenic assays with NIH-3T3 murine fibroblast cells, the MCF-7 human breast cancer cell line and the human lung adenocarcinoma cell line A549, AGS1/RASD1 markedly diminished the number of G418-resistant colonies, whereas the Ras subgroup member K-Ras was without effect. A549 cell infection with adenovirus engineered to express AGS1/RASD1 (Ad.AGS1) inhibited log phase growth in vitro and increased the percentage of cells undergoing apoptosis. The anti-growth action was also observed in vivo as the expression of AGS1/RASD1 inhibited the subcutaneous tumor growth of A549 cells in athymic nude mice. These data indicate that AGS1/RASD1, a member of the Ras superfamily of small G-proteins that often promotes cell growth and tumor expansion, plays an active role in preventing aberrant cell growth.

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Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic neurofibromas

Cited by 33 publications

References 33 publications

High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization

High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization

Molecular cytogenetic analysis in the study of brain tumors: findings and applications

The Ras-related protein AGS1/RASD1 suppresses cell growth

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