Sandya Liyanarachchi

The Ohio State University, Columbus, Ohio, United States

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Publications (72)596.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We previously showed that a long non-coding RNA (lncRNA) gene (PTCSC3) located close to the variant rs944289 that predisposes to papillary thyroid carcinoma (PTC) might target the S100A4 gene. The aim was to investigate the impact of PTCSC3 on S100A4 expression and its role in cancer development. S100A4 abundance was analyzed by qPCR in unaffected and tumor tissue from n=73 PTC patients. The expression of PTCSC3 and S100A4 was studied in BCPAP and TPC-1 cell lines with forced expression of PTCSC3 by quantitative PCR (qPCR). Expression of S100A4 target genes (VEGF and MMP-9) was studied in the BCPAP cell lines with forced expression of PTCSC3 by qPCR, reverse transcriptase PCR and Western blot. The impact of PTCSC3 on BCPAP motility and invasiveness was analyzed by the Transwell and Matrigel assays, respectively. This was a laboratory-based study using cells from clinical samples and thyroid cancer cell lines. Evidence for a link between the expression of PTCSC3 and thyroid carcinogenesis. Expression data from PTC cell lines pinpointed S100A4 as the most significantly downregulated gene in the presence of PTCSC3. S100A4 was upregulated in tumor tissue (p=9.33x10(-7)) while PTCSC3 was strongly downregulated (p=2.2x10(-16)). S100A4 transcription was moderately correlated with PTCSC3 expression in unaffected thyroid tissue (r=0.429, p=0.0001), and strongly in unaffected tissue of patients with the risk allele of rs944289 (r=0.685, p=7.88x10(-5)). S100A4, VEGF and MMP-9 were suppressed in the presence of PTCSC3 (p=0.0051, p=0.0090 and p=0.0037, respectively). PTC cells expressing PTCSC3 showed reduction in motility and invasiveness (p=4.52x10(-5) and p=1.0x10(-4), respectively). PTCSC3 downregulates S100A4 leading to a reduction in cell motility and invasiveness. We propose that PTCSC3 impacts PTC predisposition and carcinogenesis through the S100A4 pathway.
    The Journal of Clinical Endocrinology and Metabolism 08/2015; DOI:10.1210/jc.2015-2247 · 6.31 Impact Factor
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    ABSTRACT: Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analysis and other genetic criteria narrowed our list of candidates to a germline variant in the serine/arginine repetitive matrix 2 gene (SRRM2). This heterozygous variant, c.1037C > T (Ser346Phe or S346F; rs149019598) cosegregated with PTC in the family. It was not found in 138 other PTC families. It was found in 7/1,170 sporadic PTC cases and in 0/1,404 controls (p = 0.004). The encoded protein SRRM2 (also called SRm300) is part of the RNA splicing machinery. To evaluate the possibility that the S346F missense mutation affects alternative splicing, we compared RNA-Seq data in leukocytes from three mutation carriers and three controls. Significant differences in alternative splicing were identified for 1,642 exons, of which a subset of 7 exons was verified experimentally. The results confirmed a higher ratio of inclusion of exons in mutation carriers. These data suggest that the S346F mutation in SRRM2 predisposes to PTC by affecting alternative splicing of unidentified downstream target genes.
    Scientific Reports 07/2015; 5:10566. DOI:10.1038/srep10566 · 5.58 Impact Factor
  • Proceedings of the National Academy of Sciences 05/2015; 112(19):6128-6133. DOI:10.1073/pnas.1506255112 · 9.81 Impact Factor
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    ABSTRACT: Context: By genome-wide association studies (GWAS) the risk allele [A] of SNP rs965513 predisposes strongly to papillary thyroid carcinoma (PTC). It is located in a gene-poor region of 9q22 some 60kb from the FOXE1 gene. The underlying mechanisms remain to be discovered. Objective: Our objective was to identify novel transcripts in the 9q22 locus and correlate gene expression levels with the genotypes of rs965513. Design: We performed 3' and 5' RACE and RT-PCR to detect novel transcripts. One novel transcript was forcibly expressed in a cell line followed by gene expression array analysis. We genotyped rs965513 from PTC patients and measured gene expression levels by real time RT-PCR in unaffected thyroid tissue and matched tumor. Setting: This was a laboratory-based study using cells from clinical tissue samples and a cancer cell line. Main Outcome Measures: We detected previously uncharacterized transcripts and evaluated the gene expression levels and the correlation with the risk allele of rs965513, age, gender, chronic lymphocyte thyroiditis (CLT), and TSH levels. Results: We found a novel long intergenic noncoding RNA (lincRNA) gene and named it papillary thyroid cancer susceptibility candidate 2 (PTCSC2). Transcripts of PTCSC2 are downregulated in PTC tumors. The risk allele [A] of rs965513 was significantly associated with low expression of unspliced PTCSC2, FOXE1 and TSHR in unaffected thyroid tissue. We also observed a significant association of age and CLT with PTCSC2 unspliced transcript levels. The correlation between the rs965513 genotype and the PTCSC2 unspliced transcript levels remained significant after adjusting for age, gender, and CLT. Forced expression of PTCSC2 in the BCPAP cell line affected the expression of a subset of non-coding and coding transcripts with enrichment of genes functionally involved in cell cycle and cancer. Conclusions: Our data suggest a role for PTCSC2, FOXE1, and TSHR in the predisposition to PTC.
    Journal of Clinical Endocrinology &amp Metabolism 10/2014; 100(1):jc20142147. DOI:10.1210/jc.2014-2147 · 6.31 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5235-5235. DOI:10.1158/1538-7445.AM2014-5235 · 9.28 Impact Factor
  • Clinical Lymphoma, Myeloma and Leukemia 09/2014; 14:S157. DOI:10.1016/j.clml.2014.06.101 · 2.02 Impact Factor
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    ABSTRACT: Neuroblastoma rat sarcoma (RAS) viral oncogene homolog (NRAS), a small GTPase, is one of the most thoroughly studied oncogenes that controls cell growth, differentiation, and survival by facilitating signal transduction. Here, we identify four novel naturally occurring NRAS isoforms (isoforms 2-5) in addition to the canonical isoform (isoform 1). Expression analyses performed on a panel of several different human malignancies and matching normal tissue revealed distinct isoform expression patterns. Two of the novel isoforms were found in the nucleus and cytoplasm, whereas the others were exclusively cytoplasmic. The isoforms varied in their binding affinities to known downstream targets and differentially regulated the RAS signaling pathway. Strikingly, forced expression of isoform 5, which encodes only a 20-aa peptide, led to increased cell proliferation and to transformation by activation of known NRAS targets. These discoveries open new avenues in the study of NRAS.
    Proceedings of the National Academy of Sciences 02/2014; 111(11). DOI:10.1073/pnas.1401727111 · 9.81 Impact Factor
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    ABSTRACT: Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
    PLoS Genetics 02/2014; 10(2):e1004123. DOI:10.1371/journal.pgen.1004123 · 8.17 Impact Factor
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    ABSTRACT: Thyroid cancer shows high heritability but causative genes remain largely unknown. According to a common hypothesis the genetic predisposition to thyroid cancer is highly heterogeneous; being in part due to many different rare alleles. Here we used linkage analysis and targeted deep sequencing to detect a novel single-nucleotide mutation in chromosome 4q32 (4q32A>C) in a large pedigree displaying non-medullary thyroid carcinoma (NMTC). This mutation is generally ultra-rare; it was not found in 38 NMTC families, in 2676 sporadic NMTC cases or 2470 controls. The mutation is located in a long-range enhancer element whose ability to bind the transcription factors POU2F and YY1 is significantly impaired, with decreased activity in the presence of the C- allele compared with the wild type A-allele. An enhancer RNA (eRNA) is transcribed in thyroid tissue from this region and is greatly downregulated in NMTC tumors. We suggest that this is an example of an ultra-rare mutation predisposing to thyroid cancer with high penetrance.
    PLoS ONE 09/2013; 8(5):e61920. DOI:10.1371/journal.pone.0061920 · 3.23 Impact Factor
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    ABSTRACT: Background: Two recent genome-wide association studies (GWAS) identified five single nucleotide polymorphisms (SNPs) (rs965513, rs944289, rs966423, rs2439302, and rs116909374) associated with papillary thyroid carcinoma (PTC). Each variant showed highly significant but moderate to low disease risk. Here we assessed the cumulative risk and predictive value of the five SNPs. Methods: We genotyped two cohorts of individuals, 747 PTC cases and 1047 controls from Ohio, and 1795 PTC and 2090 controls from Poland. Cumulative genetic risk scores were calculated using un-weighted and weighted approaches. Results: All five SNPs showed significant association with PTC. The average cumulative risk score in cases was significantly higher than in controls (p < 2.2e-16). Each additional risk allele increased the risk of having PTC by 1.51 (95% CI, 1.4 to 1.64) in Ohio and by 1.35 (95% CI, 1.27 to 1.44) in Poland. An analysis was performed weighing risk alleles by effect size and assigning individuals to 3 weighted risk score groups, Low (<=2), Medium (2-5) and High (>5). Individuals in the High group were significantly more susceptible to PTC compared to individuals in the Low group with an odds ratio of 8.7 (95% CI, 5.8 to 13.3) in Ohio and 4.24 (95% CI, 3.10 to 5.84) in Poland. Almost identical results were obtained when follicular variant PTCs and micro PTCs were omitted. These five SNPs explain about 11% of the familial risk of thyroid cancer in the Ohio cohort and 6% in the Polish cohort. Conclusion: As the genetic risk score increases, the risk of having PTC increases. However the predictive power of the cumulative effect of these five variants is only moderately high and clinical use may not be feasible until more variants are detected.
    Thyroid: official journal of the American Thyroid Association 05/2013; 23(12). DOI:10.1089/thy.2013.0102 · 3.84 Impact Factor
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    ABSTRACT: Background:Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative.Objectives:The objective of this study was to identify susceptibility genes for PTC.Methods:A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies.Results:Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants.Conclusions:Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type.
    The Journal of Clinical Endocrinology and Metabolism 03/2013; 98(5). DOI:10.1210/jc.2012-3823 · 6.31 Impact Factor
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    ABSTRACT: Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult. We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12 years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients. Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved. Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of Cbl malabsorption. Early diagnosis improves the lifelong care required by these patients and prevents potential neurological long-term complications. This study provides the first comprehensive overview of the genetics that underlies the inherited Cbl malabsorption phenotype.
    Orphanet Journal of Rare Diseases 08/2012; 7(1):56. DOI:10.1186/1750-1172-7-56 · 3.96 Impact Factor
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    ABSTRACT: Glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy, is incurable despite the best combination of current cancer therapies. For the development of more effective therapies, discovery of novel candidate tumor drivers is urgently needed. Here, we report that peroxiredoxin 4 (PRDX4) is a putative tumor driver. PRDX4 levels were highly increased in a majority of human GBMs as well as in a mouse model of GBM. Reducing PRDX4 expression significantly decreased GBM cell growth and radiation resistance in vitro with increased levels of ROS, DNA damage, and apoptosis. In a syngenic orthotopic transplantation model, Prdx4 knockdown limited GBM infiltration and significantly prolonged mouse survival. These data suggest that PRDX4 can be a novel target for GBM therapies in the future.
    PLoS ONE 08/2012; 7(8):e42818. DOI:10.1371/journal.pone.0042818 · 3.23 Impact Factor
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    ABSTRACT: A genome-wide association study of papillary thyroid carcinoma (PTC) pinpointed two independent SNPs (rs944289 and rs965513) located in regions containing no annotated genes (14q13.3 and 9q22.33, respectively). Here, we describe a unique, long, intergenic, noncoding RNA gene (lincRNA) named Papillary Thyroid Carcinoma Susceptibility Candidate 3 (PTCSC3) located 3.2 kb downstream of rs944289 at 14q.13.3 and the expression of which is strictly thyroid specific. By quantitative PCR, PTCSC3 expression was strongly down-regulated (P = 2.84 × 10(-14)) in thyroid tumor tissue of 46 PTC patients and the risk allele (T) was associated with the strongest suppression (genotype [TT] (n = 21) vs. [CT] (n = 19), P = 0.004). In adjacent unaffected thyroid tissue, the genotype [TT] was associated with up-regulation of PTCSC3 ([TT] (n = 21) vs. [CT] (n = 19), P = 0.034). The SNP rs944289 was located in a binding site for the CCAAT/enhancer binding proteins (C/EBP) α and β. The risk allele destroyed the binding site in silico. Both C/EBPα and C/EBPβ activated the PTCSC3 promoter in reporter assays (P = 0.0009 and P = 0.0014, respectively) and the risk allele reduced the activation compared with the nonrisk allele (C) (P = 0.026 and P = 0.048, respectively). Restoration of PTCSC3 expression in PTC cell line cells (TPC-1 and BCPAP) inhibited cell growth (P = 0.002 and P = 0.019, respectively) and affected the expression of genes involved in DNA replication, recombination and repair, cellular movement, tumor morphology, and cell death. Our data suggest that SNP rs944289 predisposes to PTC through a previously uncharacterized, long intergenic noncoding RNA gene (PTCSC3) that has the characteristics of a tumor suppressor.
    Proceedings of the National Academy of Sciences 05/2012; 109(22):8646-51. DOI:10.1073/pnas.1205654109 · 9.81 Impact Factor
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    ABSTRACT: Germline mutations in PMS2 are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer. Mutation detection in PMS2 has been difficult due to the presence of several pseudogenes, but a custom-designed long-range PCR strategy now allows adequate mutation detection. Many mutations are unique. However, some mutations are observed repeatedly across individuals not known to be related due to the mutation being either recurrent, arising multiple times de novo at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with PMS2 mutations. Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here, we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations and one (c.903G>T) a probable founder. One (c.1A>G) could not be evaluated for founder mutation status. We discuss possible explanations for the frequent occurrence of founder mutations in PMS2.
    Clinical Genetics 05/2012; 83(3). DOI:10.1111/j.1399-0004.2012.01898.x · 3.65 Impact Factor
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    ABSTRACT: Mutations in the mismatch repair genes cause Lynch syndrome (LS), conferring high risk of colorectal, endometrial and some other cancers. After the same splice site mutation in the MLH1 gene (c.589-2A>G) had been observed in four ostensibly unrelated American families with typical LS cancers, its occurrence in comprehensive series of LS cases (Mayo Clinic, Germany and Italy) was determined. It occurred in 10 out of 995 LS mutation carriers (1.0%) diagnosed in the Mayo Clinic diagnostic laboratory. It did not occur among 1,803 cases tested for MLH1 mutations by the German HNPCC consortium, while it occurred in three probands and an additional five family members diagnosed in Italy. In the U.S., the splice site mutation occurs on a large (∼4.8 Mb) shared haplotype that also harbors the variant c.2146G>A, which predicts a missense change in codon 716 referred to here as V716M. In Italy, it occurs on a different, shorter shared haplotype (∼2.2 Mb) that does not carry V716M. The V716M variant was found to be present by itself in the U.S., German and Italian populations with individuals sharing a common haplotype of 280 kb, allowing us to calculate that the variant arose around 5,600 years ago (225 generations; 95% confidence interval 183-272). The splice site mutation in America arose or was introduced some 450 years ago (18 generations; 95% confidence interval 14-23); it accounts for 1.0% all LS in the Unites States and can be readily screened for.
    International Journal of Cancer 05/2012; 130(9):2088-95. DOI:10.1002/ijc.26233 · 5.01 Impact Factor
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    ABSTRACT: High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.
    Blood 04/2012; 120(2):249-58. DOI:10.1182/blood-2012-02-408492 · 10.43 Impact Factor
  • Cancer Research 04/2012; 72(8 Supplement):1307-1307. DOI:10.1158/1538-7445.AM2012-1307 · 9.28 Impact Factor
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    ABSTRACT: Overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene is implicated in myeloid leukemogenesis and associated with poor outcome in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. Additionally, high BAALC expression occurs in glioblastoma, melanoma, and childhood gastrointestinal stroma tumors, suggesting an oncogenic role for BAALC. However, the mechanisms underlying the deregulated expression are unknown. We hypothesized that a common heritable genetic feature located in cis might account for overexpression of BAALC in an allele-specific manner. By sequencing the genomic region of BAALC we identified nine informative single nucleotide polymorphisms (SNPs) and tested them for a possible association with BAALC expression levels. We show that BAALC overexpression occurs in the presence of the T allele of SNP rs62527607[GT], which creates a binding site for the activating RUNX1 transcription factor in the BAALC promoter region. The mechanism is demonstrated experimentally in vitro using luciferase reporter assays and electrophoretic mobility shift assay (EMSA) analysis. The association of high BAALC expression with the T allele and its correlations with RUNX1 expresser status are shown in vivo in a test set (n = 253) and validation set (n = 105) of samples from cytogenetically normal AML patients from different populations. Thus, we identify a heritable genomic feature predisposing to overexpression of an oncogene, thereby possibly leading to enhanced AML leukemogenesis. Our findings further suggest that genomic variants might become useful tools in the practice of personalized medicine.
    Proceedings of the National Academy of Sciences 04/2012; 109(17):6668-73. DOI:10.1073/pnas.1203756109 · 9.81 Impact Factor
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    ABSTRACT: Although the physiological basis of canonical or classical IκB kinase β (IKKβ)-nuclear factor κB (NF-κB) signaling pathway is well established, how alternative NF-κB signaling functions beyond its role in lymphoid development remains unclear. In particular, alternative NF-κB signaling has been linked with cellular metabolism, but this relationship is poorly understood. In this study, we show that mice deleted for the alternative NF-κB components IKKα or RelB have reduced mitochondrial content and function. Conversely, expressing alternative, but not classical, NF-κB pathway components in skeletal muscle stimulates mitochondrial biogenesis and specifies slow twitch fibers, suggesting that oxidative metabolism in muscle is selectively controlled by the alternative pathway. The alternative NF-κB pathway mediates this specificity by direct transcriptional activation of the mitochondrial regulator PPAR-γ coactivator 1β (PGC-1β) but not PGC-1α. Regulation of PGC-1β by IKKα/RelB also is mammalian target of rapamycin (mTOR) dependent, highlighting a cross talk between mTOR and NF-κB in muscle metabolism. Together, these data provide insight on PGC-1β regulation during skeletal myogenesis and reveal a unique function of alternative NF-κB signaling in promoting an oxidative metabolic phenotype.
    The Journal of Cell Biology 02/2012; 196(4):497-511. DOI:10.1083/jcb.201108118 · 9.69 Impact Factor

Publication Stats

3k Citations
596.88 Total Impact Points

Institutions

  • 2002–2015
    • The Ohio State University
      • • The James Comprehensive Cancer Center
      • • Department of Molecular Virology, Immunology and Medical Genetics
      • • Division of Human Genetics
      Columbus, Ohio, United States
  • 2009
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 2004
    • Columbus State University
      Columbus, Georgia, United States