LRRN2

Gene Summary

Gene:LRRN2; leucine rich repeat neuronal 2
Aliases: GAC1, LRRN5, LRANK1, FIGLER7
Location:1q32.1
Summary:The protein encoded by this gene belongs to the leucine-rich repeat superfamily. This gene was found to be amplified and overexpressed in malignant gliomas. The encoded protein has homology with other proteins that function as cell-adhesion molecules or as signal transduction receptors and is a candidate for the target gene in the 1q32.1 amplicon in malignant gliomas. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:leucine-rich repeat neuronal protein 2
HPRD
Source:NCBIAccessed: 06 August, 2015

Ontology:

What does this gene/protein do?
Show (4)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 06 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • GCGGCCGC-specific type II deoxyribonucleases
  • LRRN1
  • Deoxyribonucleases, Type II Site-Specific
  • Brain, Astrocytoma, Childhood
  • Animals, Newborn
  • Sequence Homology
  • GATC-specific type II deoxyribonucleases
  • Chromosome 1
  • Amino Acid Sequence
  • Adrenal Glands
  • Superior Cervical Ganglion
  • Brain and CNS Tumours
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Oligodendroglioma
  • Brain Stem Glioma, Childhood
  • Transcription
  • Gene Amplification
  • LRRN2
  • Cell Adhesion Molecules, Neuronal
  • Messenger RNA
  • LRRN3
  • Renin
  • Leucine
  • Proteins
  • Membrane Proteins
  • Cancer Gene Expression Regulation
  • Glioblastoma
  • Neuroblastoma
  • Gene Expression Regulation
  • myc Genes
  • Cell Differentiation
  • leucine-rich repeat proteins
  • Nerve Growth Factor
  • Neurons
Tag cloud generated 06 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: LRRN2 (cancer-related)

Arjona D, Bello MJ, Alonso ME, et al.
Real-time quantitative PCR analysis of regions involved in gene amplification reveals gene overdose in low-grade astrocytic gliomas.
Diagn Mol Pathol. 2005; 14(4):224-9 [PubMed] Related Publications
We have studied gene amplification of genes located in 1q32 (GAC1, ELF3, MDM4, and ren1), 4q11 (PDGFR-alpha), and in 12q13-14 (MDM2 and CDK4) using quantitative real-time PCR in a group of 86 tumors consisting of 44 WHO grade IV glioblastomas (GBM) (34 primary and 10 secondary tumors), 21 WHO grade III anaplastic astrocytomas (AA), and 21 WHO grade II astrocytomas (AII). Gene amplification was present in 56 of the 86 samples (65%) in at least 1 gene in our series. GAC1 (51%) and MDM4 (27%) were the most frequently amplified genes within the 1q32 amplicon, and their higher amplification frequency was statistically significant (P<0.05, chi) in the low-grade astrocytomas. Concordant co-amplification was determined for ELF3 and ren1 or ren1 and MDM4 in the grade III-IV tumors. MDM2 amplification was significantly more frequent in primary GBM (16%) than was in secondary GBM (0%). The present study shows that gene amplification in the studied regions is already present in low-grade astrocytic tumors and that amplification of some genes may represent another molecular marker to differentiate primary from secondary GBM.

Alonso ME, Bello MJ, Arjona D, et al.
Real-time quantitative PCR analysis of gene dosages reveals gene amplification in low-grade oligodendrogliomas.
Am J Clin Pathol. 2005; 123(6):900-6 [PubMed] Related Publications
Proto-oncogene amplification is an important alteration that is present in about 45% to 50% of high-grade human gliomas. We studied this mechanism in 8 genes (cyclin-dependent kinase-4 [CDK4], MDM2, MDM4, renin-angiotensin system-1, ELF3, GAC1, human epidermal growth factor receptor-2, and platelet-derived growth factor receptor-A gene) in a series of 40 oligodendrogliomas (World Health Organization (WHO) grade II, 21; WHO grade III, 13; and WHO grade II-III oligoastrocytomas, 6) using real-time quantitative polymerase chain reaction. Amplification of at least 1 of these genes was detected in 58% of samples (23/40). By histopathologic grade, 67% of grade II oligodendrogliomas (14/21), 46% of grade III anaplastic oligodendrogliomas (6/13), and 50% of mixed oligoastrocytomas (3/6) were positive for amplification of at least 1 gene. CDK4, MDM2, and GAC1 were the most frequently involved genes (12/40 [30%], 12/40 [30%], and 13/40 [33%], respectively). Our findings demonstrate gene amplification in low-grade samples indicating that it is an important alteration in the early steps of oligodendroglioma development and, therefore, might be considered a molecular mechanism leading to malignant progression toward anaplastic forms.

Hamano S, Ohira M, Isogai E, et al.
Identification of novel human neuronal leucine-rich repeat (hNLRR) family genes and inverse association of expression of Nbla10449/hNLRR-1 and Nbla10677/hNLRR-3 with the prognosis of primary neuroblastomas.
Int J Oncol. 2004; 24(6):1457-66 [PubMed] Related Publications
To search for novel prognostic indicators, we previously cloned >2,000 novel genes from primary neuroblastoma (NBL) cDNA libraries and screened for differential expression between the subsets with favorable (stage 1 or 2 with a single copy of MYCN) and unfavorable (stage 3 or 4 with amplification of MYCN) prognosis. From them, we have identified 3 genes of human neuronal leucine-rich repeat protein (NLRR) family: Nbla10449/hNLRR-1, Nbla00061/hNLRR-2/GAC1 and Nbla10677/hNLRR-3. An additional family member, hNLRR-5, was also found by homology search against public database. NLRR family proteins have been proposed to function as a neuronal adhesion molecule or soluble ligand binding receptor like Drosophila toll and slit with multiple domains including 11 sets of extracellular leucine-rich repeat (LRR)-motifs. However, the functional role of the NLRR protein family has been elusive. Our present study shows that hNLRR mRNAs are preferentially expressed in nervous system and/or adrenal gland. In cancer cell lines, hNLRR-1, hNLRR-3 and hNLRR-5 are expressed at high levels in the neural crest-derived cells. Most remarkably, in primary NBLs, hNLRR-1 is significantly expressed at high levels in unfavorable subsets as compared to favorable ones, whereas the expression pattern of hNLRR-3 and hNLRR-5 is the opposite. In order to understand the function of these receptors, we have used newborn mouse superior cervical ganglion (SCG) cells which are dependent on nerve growth factor (NGF) for their survival. Expression of the mouse counterparts of hNLRR-2 and hNLRR-3 is up-regulated after NGF-induced differentiation and down-regulated after NGF depletion-induced apoptosis. On the other hand, expression of hNLRR-1 and hNLRR-5 is inversely regulated in the same system. These results have suggested that the regulation of the hNLRR family genes may be associated with NGF signaling pathway in both SCG cells and neuroblastoma. Our quantitative real-time RT-PCR analysis using 99 primary NBLs has revealed that high levels of hNLRR-1 expression are significantly associated with older age (>1 year, p=0.0001), advanced stages (p=0.0007), low expression of TrkA (p=0.011), and MYCN amplification (p=0.0001), while those of hNLRR-3 expression are significantly correlated with the favorable prognostic indicators. Furthermore, multivariate analysis reveals that expression of hNLRR-1 is an independent prognostic indicator in human neuroblastoma. Thus, our results demonstrate that, despite being members of the same family, hNLRR-1 and hNLRR-3 may share different biological function among the NBL subsets, and that their expression level becomes novel prognostic indicators of NBL.

Riemenschneider MJ, Knobbe CB, Reifenberger G
Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target.
Int J Cancer. 2003; 104(6):752-7 [PubMed] Related Publications
We previously reported on the amplification and overexpression of the mouse double minute 4 homolog gene (MDM4) from 1q32 in a subset of malignant gliomas (Riemenschneider et al., Cancer Res 1999;59:6091-6). More recently, amplification and overexpression of the neighboring contactin 2 gene (CNTN2) was reported in individual malignant gliomas without MDM4 amplification (Rickman et al., Cancer Res 2001;61:2162-8). To address the question of whether 1q32 carries 2 independent amplification targets or a common target other than MDM4 and CNTN2, we analyzed primary malignant gliomas for amplification and overexpression of 17 different genes from this region. Our results indicate a single region of amplification that comprises the genes MDM4, GAC1, PIK3C2B and PEPP3, with only MDM4 amplification being invariably associated with overexpression. CNTN2 was found to be coamplified with MDM4 in 3 malignant gliomas but overexpressed in only 1 of these tumors. No CNTN2 amplification was detected in any of 102 malignant gliomas without MDM4 amplification. Our data therefore corroborate the notion that MDM4 is the main amplification target on 1q32 in malignant gliomas. However, coamplification and overexpression of adjacent genes may provide an additional growth advantage in some malignant gliomas with MDM4 amplification.

Herzog S, Lohmann DR, Buiting K, et al.
Marked differences in unilateral isolated retinoblastomas from young and older children studied by comparative genomic hybridization.
Hum Genet. 2001; 108(2):98-104 [PubMed] Related Publications
Although it is established that the loss of function of both alleles of the RB1 gene is a prerequisite for the development of retinoblastoma, little is known about the genetic events that are required for tumor progression. We used comparative genomic hybridization (CGH) to search for DNA copy number changes in isolated unilateral retinoblastomas. From a series of 66 patients with retinoblastomas with somatic mutations in both RB1 alleles, tumor samples from 13 children with the youngest (2.0-9.8 months) and 13 with the oldest (36.2-84.1 months) age at operation were studied. Loss at 13q14, the location of RB1, was demonstrated in two tumors only. Recurring chromosome imbalances included gains at 6p (11/26), 1q (10/26), 2p (4/26), and 17q (4/26), gains of the entire chromosome 19 (3/26), and losses at 16q (9/26). A commonly gained region at 1q32 was identified. Increased dosage of GAC1, a candidate oncogene located in 1q32, was found in two of four tumors by Southern blot analysis. Comparison of the CGH findings revealed that retinoblastomas from children with an older age at operation showed significantly more frequent (13/13 cases vs 4/13 cases; P = 0.0005) and more complex genetic abnormalities (median, 5 changes/abnormal tumor vs median, 1.5 changes/abnormal tumor; P = 0.003) than retinoblastomas from children with a young age at operation. Gains at 1q, 2p, 17q, of the entire chromosome 19 and losses of 16q were restricted to the older age group. Our results suggest that the progression of retinoblastomas from older patients follows mutational pathways different from those of younger patients.

Riemenschneider MJ, Büschges R, Wolter M, et al.
Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification.
Cancer Res. 1999; 59(24):6091-6 [PubMed] Related Publications
We have previously reported on the amplification and overexpression of the MDM2 proto-oncogene in a subset of malignant gliomas without TP53 mutation (G. Reifenberger et al, Cancer Res., 53: 2736-2739, 1993). Here, we show that the MDM4 (MDMX) gene located on 1q32 is a further target for amplification in malignant gliomas. MDM4 codes for a Mdm2-related protein that can bind to p53 and inhibits p53-mediated transcriptional transactivation. We investigated a series of 208 gliomas (106 glioblastomas, 46 anaplastic gliomas, and 56 low-grade gliomas) and identified 5 tumors (4 glioblastomas and 1 anaplastic oligodendroglioma) with MDM4 amplification and overexpression. Several other genes from 1q32 were found to be coamplified with MDM4, such as GAC1 in five tumors, REN in four tumors, and RBBP5 in three tumors. Additional analyses revealed that the malignant gliomas with MDM4 amplification and overexpression carried neither mutations in conserved regions of the TP53 gene nor amplification of the MDM2 gene. Taken together, our data indicate that amplification and overexpression of MDM4 is a novel molecular mechanism by which a small fraction of human malignant gliomas escapes p53-dependent growth control.

Almeida A, Zhu XX, Vogt N, et al.
GAC1, a new member of the leucine-rich repeat superfamily on chromosome band 1q32.1, is amplified and overexpressed in malignant gliomas.
Oncogene. 1998; 16(23):2997-3002 [PubMed] Related Publications
We have used two-dimensional electrophoresis of enzyme-digested genomic DNA to identify a novel gene GAC1, which maps at 1q32.1 and which is overexpressed in malignant gliomas in which it is amplified. GAC1 encodes a protein which belongs to the leucine-rich repeat superfamily. Amplification and overexpression of GAC1 was demonstrated in two of eight tumors where amplifications were previously evidenced by comparative genomic hybridization (one glioblastoma multiforme and one anaplastic astrocytoma), and in one of eight unselected glioblastomas multiforme. GAC1 exhibits sequence homology with other proteins which function as cell-adhesion molecules or as signal transduction receptor and is a likely candidate for the target gene in the 1q32.1 amplicon in malignant gliomas.

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Cite this page: Cotterill SJ. LRRN2 (GAC1), Cancer Genetics Web: http://www.cancer-genetics.org/GAC1.htm Accessed:

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