Research Topics
Genomes and GenesSpecies | Kimberly SiegmundSummaryAffiliation: University of Southern California Country: USA Publications
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Publications
Hierarchical clustering of lung cancer cell lines using DNA methylation markersArvind K Virmani
Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9593, USA
Cancer Epidemiol Biomarkers Prev 11:291-7. 2002..Our results show that DNA methylation patterns differ between NSCLC and SCLC cell lines and suggest that these patterns could be developed into a powerful molecular marker to achieve accurate diagnosis of lung cancer...- Ascertainment bias in family-based case-control studiesKimberly D Siegmund
Department of Preventive Medicine, University of Southern California, 1540 Alcazar Street, Suite 220, Los Angeles, CA 90089 9011, USA
Am J Epidemiol 155:875-80. 2002..This suggests that we must use caution in interpreting parameters that estimate environmental main effects from a family-based case-control study if controls are selected from outside the case-ascertainment region... - Analysis of complex methylation dataKimberly D Siegmund
Department of Preventive Medicine, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA
Methods 27:170-8. 2002..We then describe the basic statistics and bioinformatic principles relevant to the analysis of simple and complex methylation data... - A comparison of cluster analysis methods using DNA methylation dataKimberly D Siegmund
Department of Preventive Medicine, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles 90089, USA
Bioinformatics 20:1896-904. 2004..Established tools to analyze this type of data do not exist. Here, we evaluate a variety of methods for cluster analysis to determine which is most reliable... - Modeling exposures for DNA methylation profilesKimberly D Siegmund
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP 220, Los Angeles, CA 90089, USA
Cancer Epidemiol Biomarkers Prev 15:567-72. 2006..Thus, when the clusters are not identified with certainty, the extended mixture model is preferred for valid estimation of the OR and CI... 
Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancerPaul P Anglim
Department of Surgery, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089 9176, USA
Mol Cancer 7:62. 2008....
Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinomaJeffrey A Tsou
Norris Cancer Center and Department of Surgery and of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9176, USA
Mol Cancer 6:70. 2007....- Human and great ape red blood cells differ in plasmalogen levels and compositionAnn B Moser
Hugo W Moser Research Institute at Kennedy Krieger, and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lipids Health Dis 10:101. 2011..Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease... - Copy number variation in the Framingham Heart StudyCorina Shtir
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP 220, Los Angeles, California 90089, USA
BMC Proc 3:S133. 2009..Furthermore, our results indicate a relatively poor level of agreement between copy number calls resulting from the two programs. We then examined potential causes for this difference in results and the implications for future studies... - Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functionsPaul A Watkins
Department ofNeurology, Johns Hopkins University School of Medicine, Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA
BMC Physiol 10:19. 2010..Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism... - Lack of increases in methylation at three CpG-rich genomic loci in non-mitotic adult tissues during agingMichelle W Chu
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
BMC Med Genet 8:50. 2007..Somatic genomes may record their mitotic ages because greater numbers of replication errors should accumulate after greater numbers of divisions. Mitotic ages will vary between cell types if they divide at different times and rates... - Age-related human small intestine methylation: evidence for stem cell nichesJung Yeon Kim
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
BMC Med 3:10. 2005..Potentially age-related methylation also occurs in human small intestines, which would allow characterization of their stem cells and comparisons with the colon... - mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograftDarren Magda
Department of Biochemistry and Molecular Biology, University of Southern California, 2250 Alcazar Street, IGM 240, Los Angeles, CA 90089, USA
BMC Genomics 9:521. 2008..In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted rho0 counterparts grown in culture and as tumor xenografts in immune-deficient mice... - Identifying susceptibility genes by using joint tests of association and linkage and accounting for epistasisJoshua Millstein
National Oceanic and Atmospheric Administration National Marine Fisheries Service, Alaska Fisheries Science Center, 7600 Sand Point Way NE, Seattle, WA 98115, USA
BMC Genet 6:S147. 2005..The strongest effect was for SNP B03T3056, which had a median p-value of 1.98 x 10(-34). No two- or three-locus effects were found in more than one replicate... - Modeling measurement error in tumor characterization studiesCyril Rakovski
Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, California 90089 9176, USA
BMC Bioinformatics 12:284. 2011..We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon Cancer Family Registry... - Development and evaluation of new mask protocols for gene expression profiling in humans and chimpanzeesDonna M Toleno
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA
BMC Bioinformatics 10:77. 2009..In this process, only data from oligonucleotide probes predicted to have robust hybridization sensitivity and specificity for both transcriptomes are retained for analysis... - Cluster analysis for DNA methylation profiles having a detection thresholdPaul Marjoram
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
BMC Bioinformatics 7:361. 2006..This suggests that conventional clustering methodology may not perform well on this data... 
Modeling DNA methylation in a population of cancer cellsKimberly D Siegmund
USC Keck School of Medicine, University of Southern California, USA
Stat Appl Genet Mol Biol 7:Article 18. 2008..The inferred cancer trees are consistent with Gompertzian growth, a well-known cancer growth pattern...- Testing linkage disequilibrium in sibshipsK D Siegmund
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA
Am J Hum Genet 67:244-8. 2000..Finally, we concluded that although the standard analysis may lead to correct inference for practical purposes, the new test is valid, even under extreme residual familial correlation and with no cost in power at the causal locus... - Stratified case sampling and the use of family controlsK D Siegmund
Department of Preventive Medicine, University of Southern California, Los Angeles 90089 9011, USA
Genet Epidemiol 20:316-27. 2001..Overall, the most efficient study design for studying gene-environment interaction was the case-sib-control design with over-sampling of positive-family-history-cases... - Statistical approaches for the analysis of DNA methylation microarray dataKimberly D Siegmund
Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA 90089, USA
Hum Genet 129:585-95. 2011..I finish with a section describing downstream analyses of the data, focusing on methods that model percentage DNA methylation as the outcome, and methods for integrating DNA methylation with gene expression or genotype data... - Association tests in nuclear familiesK D Siegmund
Department of Preventive Medicine, University of Southern California, Los Angeles, Calif 9089 9011, USA
Hum Hered 52:66-76. 2001..They also led to equivalent power to detect linkage disequilibrium at the 5% significance level... - Repeated assessment by high-throughput assay demonstrates that sperm DNA methylation levels are highly reproducibleVictoria K Cortessis
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Fertil Steril 96:1325-30. 2011..To assess reliability of a high-throughput assay of sperm DNA methylation... - Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screeningJenny N Poynter
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033 9176, USA
Cancer Epidemiol Biomarkers Prev 17:3208-15. 2008..These results reinforce the importance of distinguishing between the underlying causes of MSI in studies of etiology and prognosis... - CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancerDaniel J Weisenberger
Department of Surgery, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
Nat Genet 38:787-93. 2006..Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors... - Diet, cancer and aging in DNA mismatch repair deficient miceJen Lan Tsao
Department of Pathology, Molecular Biology and Surgery, Norris Cancer Center, University of Southern California School of Medicine, Los Angeles, CA 90033, USA
Carcinogenesis 23:1807-10. 2002..Our studies indicate that MMR deficiency may be epistatic to certain otherwise strong environmental influences on carcinogenesis or aging... - Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human spermSahar Houshdaran
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS ONE 2:e1289. 2007..Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis... - XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma riskMariana C Stern
University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Room 5421A, Los Angeles, CA 90089, USA
Cancer Epidemiol Biomarkers Prev 15:2384-90. 2006..04). Our data suggest that the effects of smoking and alcohol may vary depending on the genetic background of proteins that participate in the base excision repair and nucleotide excision repair pathways... - Hormone therapy, DNA methylation and colon cancerAnna H Wu
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, USA
Carcinogenesis 31:1060-7. 2010..055) and increased DNA methylation of ESR1 in the 'tumorous' colonic tissues (P = 0.056). These findings on DNA methylation and hormone therapy use need confirmation in larger studies... - Older individuals appear to acquire mitotically older colorectal cancersYen Jung Woo
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
J Pathol 217:483-8. 2009..Cell division per se may be an important mechanism underlying the increased incidence of colorectal cancer with ageing, because the neoplastic phase appears more commonly to start from mitotically older crypt stem cells... - Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family RegistryJenny N Poynter
Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue, NOR4411A, Los Angeles, CA 90089 9175, USA
Cancer Res 67:11128-32. 2007..These data suggest that common variants may play important roles in the risk of CRC... - DNA repair single-nucleotide polymorphisms in colorectal cancer and their role as modifiers of the effect of cigarette smoking and alcohol in the Singapore Chinese Health StudyMariana C Stern
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Room 5421A, Los Angeles, CA 90089, USA
Cancer Epidemiol Biomarkers Prev 16:2363-72. 2007..8; 95% CI, 1.0-8.1). Our results support a role for reactive oxygen species as relevant genotoxins that may account for the effects of both smoking and alcohol on colorectal cancer risk... - XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas riskMariana C Stern
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA
Cancer Epidemiol Biomarkers Prev 14:609-15. 2005.... - Unique DNA methylation patterns distinguish noninvasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissueErika M Wolff
Department of Urology, USC Epigenome Center, and Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Cancer Res 70:8169-78. 2010..In addition, an epithelium-wide epigenetic defect in bladders with cancer might contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise... - Using DNA methylation patterns to infer tumor ancestryYou Jin Hong
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS ONE 5:e12002. 2010.... - Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patternsHyang Min Byun
Jane Anne Nohl Division of Hematology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Hum Mol Genet 18:4808-17. 2009..05). Finally, we found that the Illumina GoldenGate assay features a large number of probes (265/1505 probes, 17.6%) that contain single-nucleotide polymorphisms, which may interfere with DNA methylation analyses in genome-wide studies... - Associations between smoking, alcohol consumption, and colorectal cancer, overall and by tumor microsatellite instability statusJenny N Poynter
Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
Cancer Epidemiol Biomarkers Prev 18:2745-50. 2009..Reports have suggested that these associations may differ by tumor molecular subtype, with stronger associations for microsatellite unstable (MSI-H) tumors... - Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancersKimberly D Siegmund
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
Proc Natl Acad Sci U S A 106:4828-33. 2009..Our study illustrates the potential to reconstruct the unperturbed biology of human cancers from epigenetic passenger variations in their present-day genomes... - Inferring relative numbers of human leucocyte genome replicationsMichelle Chu
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
Br J Haematol 141:862-71. 2008..These studies tentatively support the hypothesis that methylation at certain CpG rich sequences in leucocytes could record their mitotic ages... - Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer riskAmit D Joshi
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, CA 90089, USA
Carcinogenesis 30:472-9. 2009..These findings highlight the possible contribution of diets high in red meat to the formation of lesions that elicit the NER pathway, such as carcinogen-induced bulky adducts... - Shorter androgen receptor CAG repeat lengths associated with cryptorchidism risk among Hispanic white boysCarol Davis-Dao
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Children s Hospital Los Angeles, 1441 Eastlake Avenue, MC 9175, Los Angeles, California 90033, USA
J Clin Endocrinol Metab 97:E393-9. 2012..Androgens are essential for testicular descent, and functional genetic polymorphisms in the androgen receptor gene (AR) are postulated to influence cryptorchidism risk... - Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patientsMartin G Friedrich
Departments of Urology, Clinical Pathology, and Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9176, USA
Clin Cancer Res 10:7457-65. 2004..Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues... - DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neuronsKimberly D Siegmund
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS ONE 2:e895. 2007..Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase... - Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinomaMartin G Friedrich
Department of Urology, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089 9176, USA
Eur J Cancer 41:2769-78. 2005..We identified one gene (TIMP-3) where methylation was associated with a more favourable outcome. Our data strongly support the usefulness of gene methylation as a prognostic marker in patients with non-muscle invasive bladder cancer... - Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lungJeffrey A Tsou
Norris Cancer Center and Department of Surgery and Biochemistry, Room NOR 6420, 1441 Eastlake Ave, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9176, USA
Lung Cancer 47:193-204. 2005..Our observations support the strong potential of methylation markers as tools for accurate diagnosis of neoplasms in and around the lung... - DNA methylation profile of 28 potential marker loci in malignant mesotheliomaJeffrey A Tsou
Norris Cancer Center and Department of Surgery, Keck School of Medicine, University of Southern California, Room NOR6420, 1441 Eastlake Avenue, Los Angeles, CA 90089 9176, USA
Lung Cancer 58:220-30. 2007.... - Many colorectal cancers are "flat" clonal expansionsKimberly D Siegmund
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
Cell Cycle 8:2187-93. 2009.... - A case-control study of cyclin D1 CCND1 870A-->G polymorphism and bladder cancerVictoria K Cortessis
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MC 9175, Los Angeles, CA 90033, USA
Carcinogenesis 24:1645-50. 2003..90, 95% confidence interval 0.60-1.33). The null association was not appreciably modified by bladder cancer risk factors, including lifetime smoking history, or by histopathologic classification... - Identification and functional relevance of de novo DNA methylation in cancerous B-cell populationsXiao Ming Wang
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90089, USA
J Cell Biochem 109:818-27. 2010..Furthermore, we propose that similar to de novo genetic mutations, the majority of de novo DNA methylation events observed in tumors are passengers not causally involved in tumorigenesis... - Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifenMartin Widschwendter
Department of Urology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California, 90089-9176, USA
Cancer Res 64:3807-13. 2004.... - Statistical methods for evaluating DNA methylation as a marker for early detection or prognosisTodd A Alonzo
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA
Dis Markers 23:113-20. 2007..It is important to know what factors may affect the accuracy of a marker and in which subpopulations the marker may be more accurate. Such an understanding is extremely important when comparing marker accuracy in two groups of subjects... - Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancerErika M Wolff
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 6:e1000917. 2010..These data show that, in addition to contributing to chromosomal instability, hypomethylation of LINE-1s can alter the functional transcriptome and plays a role not only in human disease but also in disease predisposition... - Testing association and linkage using affected-sib-parent study designsJoshua Millstein
National Oceanic and Atmospheric Administration National Marine Fisheries Service, Alaska Fisheries Science Center, Seattle, Washington 98115, USA
Genet Epidemiol 29:225-33. 2005..8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping...
Research Grants
- Statistical Models in EpigenomicsKimberly D Siegmund; Fiscal Year: 2010..We propose to develop mathematical models that can retrospectively reconstruct tumor histories, allowing us to address important biological questions about the growth and spread of cancer. ..
- Statistical Models in EpigenomicsKimberly Siegmund; Fiscal Year: 2005..3. Apply methods to studies of DNA methylation in colorectacl adenomas and lung cancer. ..
- Statistical Models in EpigenomicsKimberly Siegmund; Fiscal Year: 2007..4. Apply the methods to DNA methylation patterns observed in primary tumors of the colon and distant metastasis in humans and in mice. ..
- Statistical Models in EpigenomicsKimberly Siegmund; Fiscal Year: 2009..We propose to develop mathematical models that can retrospectively reconstruct tumor histories, allowing us to address important biological questions about the growth and spread of cancer. ..