12 results on '"Syeling Lai"'
Search Results
2. Prognostic Significance of p16 Cellular Localization in Oropharyngeal Squamous Cell Carcinoma
- Author
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Syeling, Lai, Ashley E, Wenaas, Vlad C, Sandulache, Christine, Hartman, Elizabeth, Chiao, Jennifer, Kramer, and Jose P, Zevallos
- Subjects
Adult ,Male ,Middle Aged ,Prognosis ,Disease-Free Survival ,Oropharyngeal Neoplasms ,Protein Transport ,Risk Factors ,Multivariate Analysis ,Humans ,Female ,Neoplasm Recurrence, Local ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Demography ,Neoplasm Staging ,Proportional Hazards Models - Abstract
p16 immunohistochemical expression serves as a surrogate for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). While HPV-positive OPSCC commonly demonstrates prominent nuclear expression, aberrant cytoplasmic expression has been demonstrated in tobacco-related head and neck cancers. The purpose of this study is to investigate the prognostic significance of p16 cellular localization in OPSCC.Retrospective cohort study and immunohistochemical expression analysis of 159 OPSCC patients treated at a tertiary-care Veterans Affairs Medical Center.All patients included in this study were male and the majority had significant tobacco (91%) and alcohol (88%) exposure. Overall, 57% of tumors were p16-positive, 32 (20%) subjects have tumors demonstrating low nuclear/low cytoplasmic (LN/LC) p16 expression, 29 (18%) high nuclear/high cytoplasmic (HN/HC) expression, 25 (16%) high nuclear/low cytoplasmic (HN/LC) expression, and 5 (3%) low nuclear/high cytoplasmic (LN/HC) expression. The 5-year disease-free survival (DFS) for the p16-negative group was 13.7%, compared to p16-positive LN/LC 28.4%, LN/HC 0%, HN/LC 74.7%, and HN/HC 93.1% (p0.0001). Overall survival for the p16-negative group was 24.2%, compared to p16-positive LN/LC 23.5%, LN/HC 0%, HN/LC 74.2%, and HN/HC 88.7% (p0.0001). On multivariable analysis, HN/HC and HN/LC expression patterns were associated with a statistically significant decreased risk of recurrence and death compared to p16-negative tumors.P16 localization has prognostic significance in OPSCC, with high nuclear expression associated with significantly better oncologic outcomes compared to low nuclear expression with high or low cytoplasmic p16 expression. P16 localization may provide additional insight into OPSCC carcinogenesis, particularly in patients with heavy tobacco exposure.
- Published
- 2016
3. Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors
- Author
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Peng, Wei, Yang, Yang, Xinjian, Guo, Nainan, Hei, Syeling, Lai, Shervin, Assassi, Mengyuan, Liu, Filemon, Tan, and Xiaodong, Zhou
- Subjects
Adult ,Male ,Polymorphism, Genetic ,Scleroderma, Systemic ,Genotype ,Dose-Response Relationship, Immunologic ,Intracellular Signaling Peptides and Proteins ,Gene Expression ,Genetic Variation ,Nuclear Proteins ,Hispanic or Latino ,Fibroblasts ,Middle Aged ,Silicon Dioxide ,Polymorphism, Single Nucleotide ,White People ,Article ,Extracellular Matrix ,Black or African American ,DNA-Binding Proteins ,Humans ,Female ,Matrix Metalloproteinase 3 ,Matrix Metalloproteinase 1 ,Tumor Necrosis Factor alpha-Induced Protein 3 - Abstract
Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype-based longitudinal association test on regions that included the loci identified.The single-nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time-course and/or dose-response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals.Our findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica-induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome-wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.
- Published
- 2015
4. Catastrophic antiphospholipid syndrome: A rare cause of disseminated microvascular thrombotic injury - a case report with pathological and molecular correlative studies
- Author
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Syeling Lai, M. Tarek Elghetany, and David H. Walker
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Multiple Organ Failure ,medicine.medical_treatment ,Autopsy ,Gene mutation ,Catastrophic antiphospholipid syndrome ,Thrombophilia ,Pathology and Forensic Medicine ,Fatal Outcome ,Antiphospholipid syndrome ,Skin Ulcer ,medicine ,Factor V Leiden ,Humans ,cardiovascular diseases ,Catastrophic Illness ,Skin ,Gangrene ,business.industry ,Microcirculation ,Thrombosis ,General Medicine ,Antiphospholipid Syndrome ,medicine.disease ,Antibodies, Antiphospholipid ,Female ,Plasmapheresis ,business - Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to small vessel thrombi in patients with positive antiphospholipid antibodies. We report a fatal case of catastrophic antiphospholipid syndrome in a young woman with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to hospital because of severe foot pain following several weeks of skin ulcerations. Doppler ultrasonography showed evidence of arterial ischemia of the both lower extremities. Despite anticoagulation, immunosuppression, plasmapheresis and antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma, ileus, and acute respiratory and renal failure that resulted in death. Autopsy showed multifocal vascular injury and microthrombi with associated hemorrhages and infarcts in multiple organs. The patient had normal levels of functional protein C and protein S and a normal level of plasma homocysteine. Tests for common thromophilic gene mutations including prothrombin 20210, factor V Leiden 1691, and methylene tetrahydrofolate reductase 677 were negative. To our knowledge, this is the first CAPS patient with molecular studies for genetic prothrombotic mutations. Our report showed that there was no association between the development of CAPS and inherited thromophilia.
- Published
- 2005
5. Impact of race on oropharyngeal squamous cell carcinoma presentation and outcomes among veterans
- Author
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Jose P, Zevallos, Vlad C, Sandulache, John, Hamblin, Heath D, Skinner, Jennifer, Kramer, Christine M, Hartman, Kelsey L, Horter, Syeling, Lai, Xiaodong, Zhou, and Elizabeth Y, Chiao
- Subjects
Adult ,Male ,Human papillomavirus 16 ,Alcohol Drinking ,Papillomavirus Infections ,Smoking ,Middle Aged ,Hospitals, Military ,Texas ,Disease-Free Survival ,White People ,Black or African American ,Oropharyngeal Neoplasms ,Risk Factors ,Carcinoma, Squamous Cell ,Humans ,Aged ,Retrospective Studies ,Veterans - Abstract
Racial disparities in oropharyngeal squamous cell carcinoma (SCC) have been demonstrated and attributed to differences in human papillomavirus (HPV) status. The purpose of this study was to examine racial disparities in oropharyngeal SCC among veterans.Retrospective review of patients with oropharyngeal SCC at a tertiary-care Veterans Affairs (VA) hospital. Adjusted Cox proportional hazards models were conducted to examine the effect of race on oropharyngeal SCC outcomes.Of 158 patients, 126 (79.7%) were white and 32 (20.3%) were African American. No difference in p16 tumor expression was noted between the groups. Five-year disease-free survival (DFS) was 42.6% and 55.1% for African Americans and whites, respectively (p = .372). Five-year overall survival (OS) for African Americans and whites was 54.6% and 51.8%, respectively (p = .768). On multivariate analysis, there was no significant difference in risk of recurrence or death by race.Racial disparities are largely ameliorated in patients with oropharyngeal SCC treated within the VA, there were no racial differences in p16 tumor expression, and outcomes remain poor.
- Published
- 2014
6. Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes
- Author
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Vlad C, Sandulache, John, Hamblin, Syeling, Lai, Todd, Pezzi, Heath D, Skinner, Numan A, Khan, Shayan M, Dioun, Christine, Hartman, Jennifer, Kramer, Elizabeth, Chiao, Xiaodong, Zhou, and Jose P, Zevallos
- Subjects
Adult ,Male ,Hospitals, Veterans ,Kaplan-Meier Estimate ,Risk Assessment ,Disease-Free Survival ,Article ,Cohort Studies ,Humans ,Neoplasm Invasiveness ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Veterans ,Smoking ,Chemoradiotherapy ,Middle Aged ,Prognosis ,Survival Analysis ,Alcoholism ,Oropharyngeal Neoplasms ,Multivariate Analysis ,Carcinogens ,Carcinoma, Squamous Cell ,Neoplasm Recurrence, Local - Abstract
A significant fraction of oropharyngeal squamous cell carcinoma (SCC) cases is associated with traditional carcinogens; in these patients, treatment response and clinical outcomes remain poor.We evaluated patient, tumor, and treatment characteristics for 200 veterans with oropharyngeal SCC treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012.Most patients (77%) were white and heavy smokers. Twenty-seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival (OS) at 5 years was 40%. Survival was impacted by T classification, treatment intensity, completion of treatment, and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with National Comprehensive Cancer Network (NCCN) guidelines.Oropharyngeal SCC in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation.
- Published
- 2014
7. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: Biological and clinical implications
- Author
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Gary L. Clayman, Jeffrey L. Myers, William F. Benedict, Syeling Lai, Adel K. El-Naggar, Jain Hua Zhou, Mario A. Luna, and Susan A. Tucker
- Subjects
Adult ,Male ,Tumor suppressor gene ,Cyclin D ,Blotting, Western ,Biology ,medicine.disease_cause ,Retinoblastoma Protein ,Pathology and Forensic Medicine ,Cyclin D1 ,medicine ,Humans ,Laryngeal Neoplasms ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Aged, 80 and over ,DNA Methylation ,Middle Aged ,Cell cycle ,Immunohistochemistry ,Squamous carcinoma ,Epidermoid carcinoma ,Mutation ,Carcinoma, Squamous Cell ,Cancer research ,biology.protein ,Female ,Mouth Neoplasms ,Carcinogenesis ,Immunostaining - Abstract
Cyclin D1, p16, and Rb genes play a critical role in the regulation of the G1-S transition of the cell cycle and are frequently altered in several neoplastic entities. Analysis of the protein products of these genes by molecular and immunohistochemical methods provides information on their functional status and allows for the phenotypic evaluation of tumor cells. We performed Western blotting and immunohistochemical analysis on tissues from 35 primary oral and laryngeal squamous carcinoma specimens with previous molecular analysis of the p16 gene and correlated the results with relevant clinicopathologic factors. Our study shows significant concordance between Western blotting and immunostaining results for cyclin D1 (P = .01), p16 proteins (P = .01), and Rb (P = .04). Heterogeneous staining of tumor cells and the positivity of non-neoplastic host elements for Rb by immunohistochemistry contributed to the discrepancy noted in some tumors by Western blotting. Significant reciprocal relationship between p16 and Rb proteins was observed (P < .001); in most tumors, absence of p16 (89%) and detectable Rb (94%) proteins were found. Two tumors had negative cyclin D1 expression, and one third overexpressed this protein. There was a lack of correlation between cyclin D1 overexpression and the clinicopathologic factors studied. Our results indicate that the absence of p16 in most of these tumors may constitute an early tumorigenic event and that the loss of the Rb function plays a minor role in HNSC.
- Published
- 1999
8. Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal cortical neoplasms
- Author
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Syeling Lai, William F. Benedict, Adel K. El-Naggar, and Susan A Silver
- Subjects
Adult ,Male ,Heterozygote ,Kidney Cortex ,Blotting, Western ,Locus (genetics) ,Biology ,medicine.disease_cause ,Retinoblastoma Protein ,Pathology and Forensic Medicine ,Loss of heterozygosity ,medicine ,Humans ,Genes, Retinoblastoma ,Aged ,Chromosome 13 ,Chromosomes, Human, Pair 13 ,Retinoblastoma ,Chromosome ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Kidney Neoplasms ,Blot ,Cancer research ,Female ,Chromosome Deletion ,Carcinogenesis - Abstract
Alteration of the retinoblastoma (RB) gene, located on chromosome 13q14, has been implicated in the pathogenesis and biological behavior of several human cancers. We investigated the RB gene status by Western blotting and immunohistochemical analysis, as well as loss of heterozygosity (LOH) at the RB locus in 21 primary human renal neoplasms (including 3 oncocytomas). In only 1 of 21 tumors was there a discrepancy between Western blot and immunochemical staining. Overall, LOH was noted in 6 of 12 informative cases. However, only one of the tumors with LOH at the RB locus had loss of RB protein expression by both Western blot and immunohistochemical analysis. Loss of RB function was found in 4 of 18 carcinomas and in none of 3 oncocytomas as determined by absent RB nuclear staining in tumor cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high-stage tumors and in patients with poor outcome. These results imply that (1) there is likely another tumor-suppressor gene on chromosome 13 involved in renal carcinogenesis, (2) LOH at chromosome 13q loci may be associated with aggressive behavior, and (3) the loss of RB function may have a role in a subset of renal carcinomas.
- Published
- 1997
9. Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma
- Author
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Syeling Lai, Randal S. Weber, Helmuth Goepfert, Adel K. El-Naggar, John G. Batsakis, M. Luna, and Xiao‐Dong ‐D Zhou
- Subjects
Adult ,Male ,Silent mutation ,Cancer Research ,Molecular Sequence Data ,Biology ,Exon ,Carcinoma ,medicine ,Humans ,Neoplastic transformation ,Gene ,Polymorphism, Single-Stranded Conformational ,Aged ,Base Sequence ,Single-strand conformation polymorphism ,Middle Aged ,Genes, p53 ,medicine.disease ,Stop codon ,Squamous carcinoma ,Oncology ,Head and Neck Neoplasms ,Mutation ,Carcinoma, Squamous Cell ,Cancer research ,Female - Abstract
Single-stranded conformation polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i)p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development. © 1995 Wiley-Liss, Inc.
- Published
- 1995
10. Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification
- Author
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Madelene M. Coombes, Bao Le, Feng Zhan, Gary L. Clayman, J. Jack Lee, Adel K. El-Naggar, Waun Ki Hong, Syeling Lai, Hyung Woo Kim, and Mario A. Luna
- Subjects
Adult ,Male ,Cancer Research ,DNA, Complementary ,Biology ,Bioinformatics ,Genome ,Gene expression ,Genetics ,Humans ,Molecular Biology ,Gene ,Aged ,Microarray analysis techniques ,Gene Expression Profiling ,Cell Differentiation ,Middle Aged ,Phenotype ,Squamous carcinoma ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Subtraction Technique ,Cancer research ,Carcinoma, Squamous Cell ,Female ,Cell Division - Abstract
The genetic events associated with the development and progression of head and neck squamous carcinoma (HNSC) are largely unknown. We analysed 12 matched pairs of histologically normal squamous mucosa and tumor specimens from six conventional and six phenotypic variants HNSC to define the differentially expressed genes in these tumors. Parallel expression analysis of 8055 unique genes was performed, and the level of the hybridization signal for each gene was measured after normalization. Hierarchical cluster analysis of the expressed genes showed distinct inter- and intra-tumoral patterns in and between conventional squamous carcinoma and squamous carcinoma variants. We also identified 26 (0.32%) differentially expressed genes that were consistently different between matched pairs of normal and tumor specimens; a selected set of the overexpressed genes was validated using real-time quantitative RT-PCR. The majority of the genes were associated with differentiation and proliferation. Our study defines a set of genes that could form the basis for the construction of limited HNSC targeted expression array and in-depth studies and further highlights gene profile differences that may be useful in pathobiologic classification of HNSC.
- Published
- 2001
11. p73 gene alterations and expression in primary oral and laryngeal squamous carcinomas
- Author
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Syeling Lai, Madelene M. Coombes, Guillermina Lozano, Scott M. Lippman, Betsy Mims, Gary L. Clayman, Mario A. Luna, and Adel K. El-Naggar
- Subjects
Silent mutation ,Adult ,Male ,Cancer Research ,Tumor suppressor gene ,Locus (genetics) ,Biology ,medicine.disease_cause ,Gene product ,Loss of heterozygosity ,Cohort Studies ,medicine ,Humans ,Genes, Tumor Suppressor ,Gene ,Laryngeal Neoplasms ,DNA Primers ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Suppressor Proteins ,Nuclear Proteins ,Tumor Protein p73 ,General Medicine ,Middle Aged ,Molecular biology ,Squamous carcinoma ,DNA-Binding Proteins ,Chromosomes, Human, Pair 1 ,Mutation ,Cancer research ,Carcinoma, Squamous Cell ,Mutagenesis, Site-Directed ,Female ,Mouth Neoplasms ,Carcinogenesis - Abstract
p73, a recently identified gene, maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. Although the gene shares sequence and functional homologies with p53, its suppressor function has not been proven. We investigated for the first time the genetic and expression status of the p73 gene and analyzed its flanking microsatellite loci on chromosome 1p36.3 in 67 primary oral and laryngeal squamous cell carcinomas to determine their association with these tumors. Our results reveal two missense mutations at codons 469 and 477 and a silent mutation at codon 349 in the C-terminal domain. Site-directed mutagenesis of p73 cDNA with these mutations and a p21 transactivation assay failed to show any significant functional consequences of these mutations. Microsatellite analysis of the flanking loci of p73 in region 1p36 showed overall alterations (loss of heterozygosity and instability) frequency of 39%, 16% at the proximal marker and 46% at the distal markers. Of the 21 cases for which we did protein expression analyses, 11 tumors had a >2-fold variation compared with matching histologically normal mucosa. Our study shows that: (i) intragenic alterations in this gene are rare and lack functional significance; (ii) its variable expression argues against a tumor suppressor function; (iii) this gene plays a minor role in head and neck squamous carcinoma; (iv) a distal site to this gene on 1p36 may harbor another suppressor gene.
- Published
- 2001
12. Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma
- Author
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Helmuth Goepfert, Waun Ki Hong, Susan A. Tucker, Gary L. Clayman, Vicki Huff, Adel K. El-Naggar, and Syeling Lai
- Subjects
Adult ,Male ,Cancer Research ,Heterozygote ,RNA, Untranslated ,Somatic cell ,Muscle Proteins ,medicine.disease_cause ,Genomic Imprinting ,Insulin-Like Growth Factor II ,Genetics ,medicine ,Humans ,Epigenetics ,Imprinting (psychology) ,Molecular Biology ,Aged ,DNA Primers ,Aged, 80 and over ,biology ,Base Sequence ,Chromosomes, Human, Pair 11 ,Homozygote ,Middle Aged ,female genital diseases and pregnancy complications ,Squamous carcinoma ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Insulin-like growth factor 2 ,embryonic structures ,biology.protein ,Cancer research ,Carcinoma, Squamous Cell ,Female ,RNA, Long Noncoding ,Carcinogenesis ,Genomic imprinting - Abstract
Genomic imprinting is an inherited epigenetic phenomenon that results in parental – origin – specific gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.
- Published
- 1999
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