Point mutation in codon 61 of N-RAS genes in human myeloma cell lines

Sawada, Makoto; Shimizu, Shiro; Arai, Toshihide; Konda, Susuma; Enomoto, Nobuyuki; Date, Taro

doi:10.1093/nar/17.21.8867

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Therefore, the methodology we propose is a protocol providing a good level of sensitivity, comparable to a recently described reliable procedure using PCR/LDR [Khanna et al, 1999]. It should also be compared to other protocols which are either very sensitive but not very reliable, such as most of the allele specific PCR including MASA [Hasegawa et al, 1995]; quite reliable but not very sensitive, such as DNA sequencing or restriction enzymes digests [Ahuja et al, 1990;Corradini et al, 1993;Portier et al, 1992;Sawada et al, 1989]; or isotopic, such as oligonucleotide hybridization [Tanaka et al, 1992]. Due to the reliable sensitivity of our approach, we can detect several mutations in a single sample showing intratumor heterogeneity for ras mutations in some cases.…”

Section: Discussionmentioning

confidence: 99%

High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis

Bézieau¹,

Devilder²,

et al. 2001

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Using allele-specific amplification method (ARMS), a highly sensitive one-stage allele-specific PCR, we have evaluated the incidence of NRAS and KRAS2 activating mutations (codons 12, 13, and 61) in 62 patients with either monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), primary plasma-cell leukemia (P-PCL), and also in human myeloma cell lines (HMCL). NRAS and/or KRAS2 mutations were found in 54.5% of MM at diagnosis (but in 81% at the time of relapse), in 50% of P-PCL, and in 50% of 16 HMCL. In contrast, the occurrence of such mutations was very low in MGUS and indolent MM (12.50%). Of note, KRAS2 mutations were always more frequent than NRAS. The validity of the technique was assessed by direct sequencing of cell lines and of some patients. Multiple mutations found in two patients were confirmed by subcloning exon PCR amplification products, testing clones with our method, and sequencing them. Thus, these early mutations could play a major role in the oncogenesis of MM and P-PCL.

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Section: Discussionmentioning

confidence: 99%

High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis

Bézieau¹,

Devilder²,

et al. 2001

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“…To determine the presence of Ras1 at larval NMJs, we used an anti-peptide antibody generated using a conserved Ras1 sequence (Sawada et al, 1989). We found that Ras immunoreactivity was concentrated at type I synaptic boutons and in the nuclei of muscle cells (Fig.…”

Section: Ras1 Is Expressed At Presynaptic Terminals and Is Involved Imentioning

confidence: 99%

The Ras1–Mitogen-Activated Protein Kinase Signal Transduction Pathway Regulates Synaptic Plasticity through Fasciclin II-Mediated Cell Adhesion

et al. 2002

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Ras proteins are small GTPases with well known functions in cell proliferation and differentiation. In these processes, they play key roles as molecular switches that can trigger distinct signal transduction pathways, such as the mitogen-activated protein kinase (MAPK) pathway, the phosphoinositide-3 kinase pathway, and the Ral-guanine nucleotide dissociation stimulator pathway. Several studies have implicated Ras proteins in the development and function of synapses, but the molecular mechanisms for this regulation are poorly understood. Here, we demonstrate that the Ras-MAPK pathway is involved in synaptic plasticity at the Drosophila larval neuromuscular junction. Both Ras1 and MAPK are expressed at the neuromuscular junction, and modification of their activity levels results in an altered number of synaptic boutons. Gain- or loss-of-function mutations in Ras1 and MAPK reveal that regulation of synapse structure by this signal transduction pathway is dependent on fasciclin II localization at synaptic boutons. These results provide evidence for a Ras-dependent signaling cascade that regulates fasciclin II-mediated cell adhesion at synaptic terminals during synapse growth.

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Identification of a Second Conserved Element Within the Coding Sequence of a Mouse H3 Histone Gene That Interacts With Nuclear Factors and Is Necessary for Normal Expression

Kaludov

Pabón‐Peña

Hurt

1996

Nucleic Acids Research

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Replication-dependent histone genes of all four nucleosomal classes are coordinately up-regulated at the beginning of S phase of the eukaryotic cell cycle. The universality and importance of this process in eukaryotic cells suggest that common regulatory mechanisms are involved in controlling the high level of expression of these histone genes. We have previously identified the alpha element within mouse H2a.2 and H3.2 coding region activating sequences (CRAS), which is involved in regulation of these two replication-dependent genes. Here we report the identification of a second element within the mouse histone CRAS, the omega element. This element interacts with nuclear proteins and we present in vivo evidence that this sequence is required for normal expression. Omega nucleotides involved in interaction with nuclear proteins have been precisely mapped by menas of DNase I footprinting and methylation interference assays. A naturally occurring mutation in the omega sequence is found in a replication-independent H3.3 gene. Mutation of the H3.2 omega element to that of the H3.3 sequence (3 nt changes) caused a 4-fold drop in in vivo expression of the H3.2 gene in stably transfected CHO cells, equally the effect of mutation of all 7 nt of the element. By UV cross-linking we have determined the approximate molecular weight of the omega binding protein to be 45 kDa. Finally, we identify putative omega sequences in the coding region of mouse H2B and H4 histone genes.

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Point mutation in codon 61 of N-RAS genes in human myeloma cell lines

Cited by 3 publications

References 6 publications

High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis

High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis

The Ras1–Mitogen-Activated Protein Kinase Signal Transduction Pathway Regulates Synaptic Plasticity through Fasciclin II-Mediated Cell Adhesion

Identification of a Second Conserved Element Within the Coding Sequence of a Mouse H3 Histone Gene That Interacts With Nuclear Factors and Is Necessary for Normal Expression

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