The Experts below are selected from a list of 34446 Experts worldwide ranked by ideXlab platform
John D. Minna - One of the best experts on this subject based on the ideXlab platform.
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identification of Chromosome Arm 9p as the most frequent target of homozygous deletions in lung cancer
Genes Chromosomes and Cancer, 2005Co-Authors: Masamitsu Sato, John D. Minna, Jun Yokota, Kenji Takahashi, Kazuhiro Nagayama, Yasuhito Arai, Mitsumasa Okada, Takashi KohnoAbstract:Genome scanning at a 1-Mb resolution was undertaken in 29 lung cancer cell lines to clarify the distribution of homozygous (i.e., both allele) deletions along lung cancer genomes, using a high-resolution single nucleotide polymorphism array. Eighteen regions, including two known tumor suppressor loci, CDKN2A at 9p21 and FHIT at 3p14, were found homozygously deleted. Frequencies of deletions at the 18 regions were evaluated by genomic polymerase chain reaction in 78 lung cancer cell lines. Seven regions, 2q24, 3p14, 5q11, 9p21, 9p23, 11q14, and 21q21, were homozygously deleted in two or more cell lines. The CDKN2A locus at 9p21 was most frequently deleted (20/78, 26%), and the deletions were detected exclusively in non-small-cell lung carcinomas (NSCLCs). The PTPRD (protein tyrosine phosphatase receptor type D) locus at 9p23 was the second-most frequently deleted (8/78, 10%), and the deletions were detected in both small-cell lung carcinomas (SCLC) and NSCLC. In addition, the 9p24 region was deleted in a NSCLC. In total, 24 (31%) cell lines carried at least one deletion on Chromosome Arm 9p, while deletions on the remaining Chromosome Arms were observed at most in four (5%) cell lines. Deletions at 9p24, 9p23, and 9p21 were not contiguous with one another, and preferential co-occurrence or mutual exclusiveness for the deletions at these three loci was not observed. Thus, it was indicated that 9p is the most frequent target of homozygous deletions in lung cancer, suggesting that the Arm contains multiple lung tumor suppressor genes and/or genomic features fragile during lung carcinogenesis. © 2005 Wiley-Liss, Inc.
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genomic and gene expression profiling of minute alterations of Chromosome Arm 1p in small cell lung carcinoma cells
British Journal of Cancer, 2005Co-Authors: Laura Jane Henderson, Adi F. Gazdar, John D. Minna, Luc Girard, Calum MacaulayAbstract:Genetic alterations occurring on human Chromosome Arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this Arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial Chromosome clones spanning the 120 megabase (Mb) 1p Arm from 1p11.2 to p36.33. The 1p Arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this Arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2–p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase–polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Bradley P. Coe, Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Calum Macaulay, Wan L. LamAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Calum E MacaulayAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes. © 2004 Wiley-Liss, Inc.
Laura Jane Henderson - One of the best experts on this subject based on the ideXlab platform.
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genomic and gene expression profiling of minute alterations of Chromosome Arm 1p in small cell lung carcinoma cells
British Journal of Cancer, 2005Co-Authors: Laura Jane Henderson, Adi F. Gazdar, John D. Minna, Luc Girard, Calum MacaulayAbstract:Genetic alterations occurring on human Chromosome Arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this Arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial Chromosome clones spanning the 120 megabase (Mb) 1p Arm from 1p11.2 to p36.33. The 1p Arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this Arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2–p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase–polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Bradley P. Coe, Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Calum Macaulay, Wan L. LamAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Calum E MacaulayAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes. © 2004 Wiley-Liss, Inc.
Adi F. Gazdar - One of the best experts on this subject based on the ideXlab platform.
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genomic and gene expression profiling of minute alterations of Chromosome Arm 1p in small cell lung carcinoma cells
British Journal of Cancer, 2005Co-Authors: Laura Jane Henderson, Adi F. Gazdar, John D. Minna, Luc Girard, Calum MacaulayAbstract:Genetic alterations occurring on human Chromosome Arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this Arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial Chromosome clones spanning the 120 megabase (Mb) 1p Arm from 1p11.2 to p36.33. The 1p Arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this Arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2–p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase–polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Bradley P. Coe, Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Calum Macaulay, Wan L. LamAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Calum E MacaulayAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes. © 2004 Wiley-Liss, Inc.
Calum Macaulay - One of the best experts on this subject based on the ideXlab platform.
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genomic and gene expression profiling of minute alterations of Chromosome Arm 1p in small cell lung carcinoma cells
British Journal of Cancer, 2005Co-Authors: Laura Jane Henderson, Adi F. Gazdar, John D. Minna, Luc Girard, Calum MacaulayAbstract:Genetic alterations occurring on human Chromosome Arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this Arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial Chromosome clones spanning the 120 megabase (Mb) 1p Arm from 1p11.2 to p36.33. The 1p Arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this Arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2–p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase–polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.
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high resolution Chromosome Arm 5p array cgh analysis of small cell lung carcinoma cell lines
Genes Chromosomes and Cancer, 2005Co-Authors: Bradley P. Coe, Laura Jane Henderson, Cathie Garnis, Ming-sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Calum Macaulay, Wan L. LamAbstract:Genomic amplification of regions on Chromosome Arm 5p has been observed frequently in small cell lung cancer (SCLC), implying the presence of multiple oncogenes on this Arm. Although conventional comparative genomic hybridization (CGH) detects gross chromosomal copy number changes, gene discovery requires a higher-resolution approach in order to identify regions of alteration precisely. To identify candidate genes on this Chromosome Arm, we developed a high-resolution, 10-clone-per-megabase bacterial artificial Chromosome CGH array for 5p and examined a panel of 15 SCLC cell lines. Utilization of this CGH array has allowed the fine-mapping of breakpoints to regions as small as 200 kb in a single experiment. In addition to reporting our observations of aberrations at the well-characterized SKP2 and TERT loci, we describe the identification of microdeletions that have escaped detection by conventional screens and the identification TRIO and ANKH as novel putative oncogenes.
Bradley J. White - One of the best experts on this subject based on the ideXlab platform.
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Chromosome Arm specific patterns of polymorphism associated with chromosomal inversions in the major african malaria vector anopheles funestus
Molecular Ecology, 2017Co-Authors: Colince Kamdem, Caroline Fouet, Bradley J. WhiteAbstract:Chromosomal inversions facilitate local adaptation of beneficial mutations and modulate genetic polymorphism, but the extent of their effects within the genome is still insufficiently understood. The genome of Anopheles funestus, a malaria mosquito endemic to sub-Saharan Africa, contains an impressive number of paracentric polymorphic inversions, which are unevenly distributed among Chromosomes and provide an excellent framework for investigating the genomic impacts of chromosomal rearrangements. Here we present results of a fine-scale analysis of genetic variation within the genome of two weakly differentiated populations of Anopheles funestus inhabiting contrasting moisture conditions in Cameroon. Using population genomic analyses, we found that genetic divergence between the two populations is centered on regions of the genome corresponding to three inversions, which are characterized by high values of FST, absolute sequence divergence and fixed differences. Importantly, in contrast to the 2L Chromosome Arm, which is collinear, nucleotide diversity is significantly reduced along the entire length of three autosome Arms bearing multiple overlapping chromosomal rearrangements. These findings support the idea that interactions between reduced recombination and natural selection within inversions contribute to sculpt nucleotide polymorphism across Chromosomes in An. funestus. This article is protected by copyright. All rights reserved.
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Chromosome Arm specific patterns of polymorphism associated with chromosomal inversions in the major african malaria vector anopheles funestus
bioRxiv, 2017Co-Authors: Colince Kamdem, Caroline Fouet, Bradley J. WhiteAbstract:Chromosomal inversions facilitate local adaptation of beneficial mutations and modulate genetic polymorphism, but the extent of their effects within the genome is still insufficiently understood. The genome of Anopheles funestus, a malaria mosquito endemic to sub-Saharan Africa, contains an impressive number of paracentric polymorphic inversions, which are unevenly distributed among Chromosomes and provide an excellent framework for investigating the genomic impacts of chromosomal rearrangements. Here we present results of a fine-scale analysis of genetic variation within the genome of two weakly differentiated populations of Anopheles funestus inhabiting contrasting moisture conditions in Cameroon. Using population genomic analyses, we found that genetic divergence between the two populations is centered on regions of the genome corresponding to three inversions, which are characterized by high values of FST, absolute sequence divergence and fixed differences. Importantly, in contrast to the 2L Chromosome Arm, which is collinear, nucleotide diversity is significantly reduced along the entire length of three autosome Arms bearing multiple overlapping chromosomal rearrangements. These findings support the idea that interactions between reduced recombination and natural selection within inversions contribute to sculpt nucleotide polymorphism across Chromosomes in An. funestus.
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Chromosomal inversions drive Chromosome Arm specific patterns of polymorphism in the major African malaria vector, Anopheles funestus
bioRxiv, 2017Co-Authors: Colince Kamdem, Caroline Fouet, Bradley J. WhiteAbstract:Chromosomal inversions facilitate local adaptation of beneficial mutations and modulate genetic polymorphism, but the extent of their effects within the genome is not fully resolved. The genome of Anopheles funestus, a malaria mosquito endemic to sub-Saharan Africa, contains an impressive number of paracentric polymorphic inversions, which are unevenly distributed among Chromosomes and provide an excellent framework for investigating the genomic impacts of chromosomal rearrangements. Here we present results of a fine-scale analysis of genetic variation within the genome of two Anopheles funestus ecotypes present in Cameroon. Specifically, we used FST outlier and population genomic analyses to highlight the strong relationship that exists between the presence of inversions and the genomic patterns of divergence and polymorphism in this mosquito. We found evidence that local adaptation in this geographic area is driven by divergent selection within three polymorphic chromosomal inversions, which segregate between savannah and forest ecosystems. Importantly, in contrast to the 2L Chromosome Arm, which is collinear, nucleotide diversity is significantly reduced along the entire length of three autosome Arms bearing multiple overlapping chromosomal rearrangements. These findings support the idea that interactions between reduced recombination and selection within chromosomal rearrangements contribute to sculpt nucleotide polymorphism across entire Chromosomes in An. funestus.