Novel Regions (novel + regions)

Distribution by Scientific Domains


Selected Abstracts


Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia

GENES, CHROMOSOMES AND CANCER, Issue 9 2008
Manu Gupta
The acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15,55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate-risk group as defined by cytogenetics. All cases with a high FLT3 -ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3 -ITD - /FLT3 -TKD+ mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets. 2008 Wiley-Liss, Inc. [source]


KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2007
N. C. Goddard
Summary Testicular germ cell tumours (TGCTs) are the leading cause of cancer deaths in young male Caucasians. Identifying changes in DNA copy number can pinpoint genes involved in tumour development. We defined the smallest overlapping regions of imbalance in TGCTs using array comparative genomic hybridization analysis. Novel regions, or regions which refined those previously reported, were identified. The expression profile of genes from 12p, which is invariably gained in TGCTs, and amplicons defined at 12p11.2-12.1 and 4q12, suggest KRAS and KIT involvement in TGCT and seminoma development, respectively. Amplification of these genes was not found in intratubular germ cell neoplasia adjacent to invasive disease showing these changes, suggesting their involvement in tumour progression. Activating mutations of RAS genes (KRAS or NRAS) and overexpression of KRAS were mutually exclusive events. These, correlations between the expression levels of KIT, KRAS and GRB7 (which encodes an adapter molecule known to interact with the KIT tyrosine kinase receptor) and other reported evidence reviewed here, are consistent with a role for activation of KIT and RAS signalling in TGCT development. In order to assess a role for KIT in seminomas, we modulated the level of KIT expression in TCam-2, a seminoma cell line. The likely seminomatous origin of this cell line was supported by demonstrating KIT and OCT3/4 overexpression and gain of 12p material. Reducing the expression of KIT in TCam-2 through RNA inhibition resulted in decreased cell viability. Further understanding of KIT and RAS signalling in TGCTs may lead to novel therapeutic approaches for these tumours. [source]


Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia

GENES, CHROMOSOMES AND CANCER, Issue 9 2008
Manu Gupta
The acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15,55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate-risk group as defined by cytogenetics. All cases with a high FLT3 -ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3 -ITD - /FLT3 -TKD+ mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets. 2008 Wiley-Liss, Inc. [source]


Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss

GENES, CHROMOSOMES AND CANCER, Issue 3 2003
D. J. Simpson
Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor-suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome-wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non-functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre-amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole-genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non-invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non-functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non-functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non-invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non-invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome-wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype-specific and were found at a higher frequency in invasive tumors than in their non-invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype-specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple "hotspots" throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic-mediated gene-silencing events. 2003 Wiley-Liss, Inc. [source]


Molecular cytogenetic characterization of non-Hodgkin lymphoma cell lines

GENES, CHROMOSOMES AND CANCER, Issue 3 2002
Sukvarsha Mehra
Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) have greatly enhanced the resolution of cytogenetic analysis, enabling the identification of novel regions of rearrangement and amplification in tumor cells. Here we report the analysis of 10 malignant non-Hodgkin lymphoma (NHL) cell lines derived at the Ontario Cancer Institute (OCI), Toronto, designated as OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-LY4, OCI-Ly7, OCI-Ly8, OCI-Ly12, OCI-Ly13.2, OCI-Ly17, and OCI-Ly18, by G-banding, SKY, and CGH, and we present their comprehensive cytogenetic profiles. In contrast to the 52 breakpoints identified by G-banding, SKY identified 87 breakpoints, which clustered at 1q21, 7p15, 8p11, 13q21, 13q32, 14q32, 17q11, and 18q21. G-banding identified 10 translocations, including the previously described recurring translocations, t(8;14)(q24;q32) and t(14;18)(q32;q21). In contrast, SKY identified 60 translocations, including five that were recurring, t(8;14)(q24;q32), t(14;18)(q32;q21), t(4;7)(p12;q22), t(11;18)(q22;q21), and t(3;18)(q21;p11). SKY also identified the source of all the marker chromosomes. In addition, 10 chromosomes that were classified as normal by G-banding were found by SKY to be rearranged. CGH identified seven sites of high-level DNA amplification, 1q31-32, 2p12-16, 8q24, 11q23-25, 13q21-22, 13q32-34, and 18q21-23; of these, 1q31-32, 11q23-25, 13q21-22, and 13q32-34 have previously not been described as amplified in NHL. This comprehensive cytogenetic characterization of 10 NHL cell lines identified novel sites of rearrangement and amplification; it also enhances their value in experimental studies aimed at gene discovery and gene function. 2002 Wiley-Liss, Inc. [source]


Perceptual Organization Based on Common Region in Infancy

INFANCY, Issue 2 2007
Ramesh S. Bhatt
We examined whether infants organize information according to the newly proposed principle of common region, which states that elements within a region are grouped together and separated from those of other regions. In Experiment 1, 6- to 7-month-olds exhibited sensitivity to regions by discriminating between the displacement of an element within a region versus across regions. In Experiments 2 (6- to 7-month-olds) and 3 (3- to 4-month-olds), infants who were habituated to 2 elements in each of 2 regions subsequently discriminated between a familiar and novel grouping in familiar and novel regions. Thus, infants as young as 3 to 4 months of age are not only sensitive to regions in visual images, but also use these regions to group elements in accord with the principle of common region. Because common region analysis is critical to such basic visual functions as figure-ground and object segregation, these results suggest that the organizational mechanism that underlies many vital visual functions is already operational by 3 to 4 months of age. [source]


High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2006
Cathie Garnis
Abstract Chromosomal regions harboring tumor suppressors and oncogenes are often deleted or amplified. Array comparative genomic hybridization detects segmental DNA copy number alterations in tumor DNA relative to a normal control. The recent development of a bacterial artificial chromosome array, which spans the human genome in a tiling path manner with >32,000 clones, has facilitated whole genome profiling at an unprecedented resolution. Using this technology, we comprehensively describe and compare the genomes of 28 commonly used non-small cell lung carcinoma (NSCLC) cell models, derived from 18 adenocarcinomas (AC), 9 squamous cell carcinomas and 1 large cell carcinoma. Analysis at such resolution not only provided a detailed genomic alteration template for each of these model cell lines, but revealed novel regions of frequent duplication and deletion. Significantly, a detailed analysis of chromosome 7 identified 6 distinct regions of alterations across this chromosome, implicating the presence of multiple novel oncogene loci on this chromosome. As well, a comparison between the squamous and AC cells revealed alterations common to both subtypes, such as the loss of 3p and gain of 5p, in addition to multiple hotspots more frequently associated with only 1 subtype. Interestingly, chromosome 3q, which is known to be amplified in both subtypes, showed 2 distinct regions of alteration, 1 frequently altered in squamous and 1 more frequently altered in AC. In summary, our data demonstrate the unique information generated by high resolution analysis of NSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes. 2005 Wiley-Liss, Inc. [source]


Genome-wide identification of quantitative trait loci for carcass composition and meat quality in a large-scale White Duroc Chinese Erhualian resource population

ANIMAL GENETICS, Issue 5 2009
J. Ma
Summary Carcass and meat quality traits are economically important in pigs. In this study, 17 carcass composition traits and 23 meat quality traits were recorded in 1028 F2 animals from a White Duroc Erhualian resource population. All pigs in this experimental population were genotyped for 194 informative markers covering the entire porcine genome. Seventy-seven genome-wide significant quantitative trait loci (QTL) for carcass traits and 68 for meat quality were mapped to 34 genomic regions. These results not only confirmed many previously reported QTL but also revealed novel regions associated with the measured traits. For carcass traits, the most prominent QTL was identified for carcass length and head weight at 57 cM on SSC7, which explained up to 50% of the phenotypic variance and had a 95% confidence interval of only 3 cM. Moreover, QTL for kidney and spleen weight and lengths of cervical vertebrae were reported for the first time in pigs. For meat quality traits, two significant QTL on SSC5 and X were identified for both intramuscular fat content and marbling score in the longissimus muscle, while three significant QTL on SSC1 and SSC9 were found exclusively for IMF. Both LM and the semimembranous muscle showed common QTL for colour score on SSC4, 5, 7, 8, 13 and X and discordant QTL on other chromosomes. White Duroc alleles at a majority of QTL detected were favourable for carcass composition, while favourable QTL alleles for meat quality originated from both White Duroc and Erhualian. [source]