The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Paul J Van Diest - One of the best experts on this subject based on the ideXlab platform.
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simultaneous Chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma
Modern Pathology, 2004Co-Authors: Fulvia Farabegoli, Mario A J A Hermsen, Claudio Ceccarelli, Donatella Santini, Marianne M Weiss, Gerrit A Meijer, Paul J Van DiestAbstract:We applied comparative genomic hybridization (CGH) to 46 breast carcinoma samples, collected from 1993 to 1995, in order to detect Chromosome 1q gains and 16q losses and to define whether samples showing both these alterations had distinct biopathologic features and different clinical outcome. A total of 22 samples (48%) had simultaneous Chromosome 1q gain and 16q loss, which was always associated with other genetic changes. In total, 23 samples had various Chromosome imbalances (including Chromosome 1q gain independent of Chromosome 16q loss and vice versa) and one sample did not show detectable alterations. Samples having Chromosome 1q gain/16q loss were compared to the other samples with regard to neoplasm size, lymph-node status, histologic and nuclear grade, estrogen and progesterone receptor presence, Ki-67, pRB, Cyclin D1, Cyclin A, p53, p21 and p27 expression as detected by immunohistochemistry. The samples showing Chromosome 1q gain/16q loss had high steroid hormone receptor expression (P=0.02), low cell growth fraction (Ki-67, P=0.03) and high p27 expression (P<0.001). No statistical correlation with disease-free survival and overall survival or response to hormonal therapy was found. We conclude that simultaneous Chromosome 1q gain/16q loss is a frequent event in invasive breast cancer, which occurs in a subset of both intermediate- and high-grade breast carcinomas. Although the final Chromosome 1q and 16q imbalances might have originated from different Chromosome alterations in low- and high-grade samples, the gene–dosage effect might be important in conferring peculiar biopathologic characteristics to this subset of samples. The cytogenetic and molecular mechanisms underlying these Chromosome changes deserve further investigations.
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simultaneous Chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma
Modern Pathology, 2004Co-Authors: Fulvia Farabegoli, Mario A J A Hermsen, Claudio Ceccarelli, Donatella Santini, Marianne M Weiss, Gerrit A Meijer, Paul J Van DiestAbstract:Simultaneous Chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma
Jeffrey A Knauf - One of the best experts on this subject based on the ideXlab platform.
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genomic alterations in fatal forms of non anaplastic thyroid cancer identification of med12 and rbm10 as novel thyroid cancer genes associated with tumor virulence
Clinical Cancer Research, 2017Co-Authors: Tihana Ibrahimpasic, Shyam Deraje, Diane L Carlson, Snjezana Dogan, Iñigo Landa, Jocelyn C. Migliacci, Sumit Middha, Venkatraman E. Seshan, Bin Xu, Jeffrey A KnaufAbstract:Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC). Results. There was a very high prevalence of TERT promoter mutations, comparable to that of anaplastic thyroid cancer, and these co-occurred with BRAF and RAS mutations. A high incidence of Chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 were identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared to the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. Conclusions. These data support a model whereby fatal non-anaplastic thyroid cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations and Chromosome 1q gain highlight their likely association with tumor virulence.
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genomic alterations in fatal forms of non anaplastic thyroid cancer identification of med12 and rbm10 as novel thyroid cancer genes associated with tumor virulence
Clinical Cancer Research, 2017Co-Authors: Tihana Ibrahimpasic, Shyam Deraje, Diane L Carlson, Jeffrey A Knauf, Snjezana Dogan, Iñigo Landa, Jocelyn C. Migliacci, Sumit Middha, Venkatraman E. Seshan, Brian R UntchAbstract:Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of Chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and Chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970-80. ©2017 AACR.
Tihana Ibrahimpasic - One of the best experts on this subject based on the ideXlab platform.
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genomic alterations in fatal forms of non anaplastic thyroid cancer identification of med12 and rbm10 as novel thyroid cancer genes associated with tumor virulence
Clinical Cancer Research, 2017Co-Authors: Tihana Ibrahimpasic, Shyam Deraje, Diane L Carlson, Snjezana Dogan, Iñigo Landa, Jocelyn C. Migliacci, Sumit Middha, Venkatraman E. Seshan, Bin Xu, Jeffrey A KnaufAbstract:Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC). Results. There was a very high prevalence of TERT promoter mutations, comparable to that of anaplastic thyroid cancer, and these co-occurred with BRAF and RAS mutations. A high incidence of Chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 were identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared to the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. Conclusions. These data support a model whereby fatal non-anaplastic thyroid cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations and Chromosome 1q gain highlight their likely association with tumor virulence.
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genomic alterations in fatal forms of non anaplastic thyroid cancer identification of med12 and rbm10 as novel thyroid cancer genes associated with tumor virulence
Clinical Cancer Research, 2017Co-Authors: Tihana Ibrahimpasic, Shyam Deraje, Diane L Carlson, Jeffrey A Knauf, Snjezana Dogan, Iñigo Landa, Jocelyn C. Migliacci, Sumit Middha, Venkatraman E. Seshan, Brian R UntchAbstract:Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of Chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and Chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970-80. ©2017 AACR.
Siu L Hui - One of the best experts on this subject based on the ideXlab platform.
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identification of a linkage disequilibrium block in Chromosome 1q associated with bmd in premenopausal white women
Journal of Bone and Mineral Research, 2008Co-Authors: Shoji Ichikawa, Daniel L Koller, Leah R Curry, Dongbing Lai, Xiaoling Xuei, Elizabeth W Pugh, Ya Yu Tsai, Kimberly F Doheny, Howard J Edenberg, Siu L HuiAbstract:Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of Chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10−6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p 2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in Chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.
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confirmation of linkage to Chromosome 1q for peak vertebral bone mineral density in premenopausal white women
American Journal of Human Genetics, 2004Co-Authors: Michael J Econs, Daniel L Koller, Siu L Hui, Tonya Fishburn, Michael P Conneally, Conrad C Johnston, Munro Peacock, Tatiana ForoudAbstract:Peak bone mineral density (BMD) is a highly heritable trait and is a good predictor of the risk of osteoporosis and fracture in later life. Recent studies have sought to identify the genes underlying peak BMD. Linkage analysis in a sample of 464 premenopausal white sister pairs detected linkage of spine BMD to Chromosome 1q (LOD 3.6). An independent sample of 254 white sister pairs has now been genotyped, and it also provides evidence of linkage to Chromosome 1q (LOD 2.5) for spine BMD. Microsatellite markers were subsequently genotyped for a 4-cM map in the Chromosome 1q region in all available white sister pairs (n=938), and a LOD score of 4.3 was obtained near the marker D1S445. Studies in the mouse have also detected evidence of linkage to BMD phenotypes in the region syntenic to our linkage finding on Chromosome 1q. Thus, we have replicated a locus on 1q contributing to BMD at the spine and have found further support for the region in analyses employing an enlarged sample. Studies are now ongoing to identify the gene(s) contributing to peak spine BMD in women.
Eleftheria Zeggini - One of the best experts on this subject based on the ideXlab platform.
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linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal on Chromosome 1q
Diabetes, 2009Co-Authors: Inga Prokopenko, Braxton D Mitchell, Eleftheria Zeggini, Robert L Hanson, Leslie J Baier, William N Rayner, Pelin Akan, Swapan K DasAbstract:OBJECTIVE Linkage of the Chromosome 1q21–25 region to type 2 diabetes has been demonstrated in multiple ethnic groups. We performed common variant fine-mapping across a 23-Mb interval in a multiethnic sample to search for variants responsible for this linkage signal. RESEARCH DESIGN AND METHODS In all, 5,290 single nucleotide polymorphisms (SNPs) were successfully genotyped in 3,179 type 2 diabetes case and control subjects from eight populations with evidence of 1q linkage. Samples were ascertained using strategies designed to enhance power to detect variants causal for 1q linkage. After imputation, we estimate ∼80% coverage of common variation across the region ( r 2 > 0.8, Europeans). Association signals of interest were evaluated through in silico replication and de novo genotyping in ∼8,500 case subjects and 12,400 control subjects. RESULTS Association mapping of the 23-Mb region identified two strong signals, both of which were restricted to the subset of European-descent samples. The first mapped to the NOS1AP ( CAPON ) gene region (lead SNP: rs7538490, odds ratio 1.38 [95% CI 1.21–1.57], P = 1.4 × 10 −6 , in 999 case subjects and 1,190 control subjects); the second mapped within an extensive region of linkage disequilibrium that includes the ASH1L and PKLR genes (lead SNP: rs11264371, odds ratio 1.48 [1.18–1.76], P = 1.0 × 10 −5 , under a dominant model). However, there was no evidence for association at either signal on replication, and, across all data (>24,000 subjects), there was no indication that these variants were causally related to type 2 diabetes status. CONCLUSIONS Detailed fine-mapping of the 23-Mb region of replicated linkage has failed to identify common variant signals contributing to the observed signal. Future studies should focus on identification of causal alleles of lower frequency and higher penetrance.
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Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to Chromosome 1q.
Diabetes, 2006Co-Authors: Eleftheria Zeggini, Coleen M Damcott, Robert L Hanson, Mohammad A Karim, N William Rayner, Christopher J Groves, Leslie J Baier, Terri C Hale, Andrew T Hattersley, Graham A HitmanAbstract:The gene encoding the transcription factor upstream stimulatory factor (USF)1 influences susceptibility to familial combined hyperlipidemia (FCHL) and triglyceride levels. Phenotypic overlap between FCHL and type 2 diabetes makes USF1 a compelling positional candidate for the widely replicated type 2 diabetes linkage signal on Chromosome 1q. We typed 22 variants in the F11R/USF1 region (1 per 3 kb), including those previously implicated in FCHL-susceptibility (or proxies thereof) in 3,726 samples preferentially enriched for 1q linkage. We also examined glucose- and lipid-related continuous traits in an overlapping set of 1,215 subjects of European descent. There was no convincing evidence for association with type 2 diabetes in any of seven case-control comparisons, individually or combined. Family-based association analyses in 832 Pima subjects were similarly negative. At rs3737787 (the variant most strongly associated with FCHL), the combined odds ratio, per copy of the rarer A-allele, was 1.10 (95% CI 0.97-1.24, P = 0.13). In 124 Utah subjects, rs3737787 was significantly associated (P = 0.002) with triglyceride levels, but direction of this association was opposite to previous reports, and there was no corroboration in three other samples. These data exclude USF1 as a major contributor to type 2 diabetes susceptibility and the basis for the Chromosome 1q linkage. They reveal only limited evidence for replication of USF1 effects on continuous metabolic traits.