37 results on '"Fahcina Lawson"'
Search Results
2. Supplementary Figure 6A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
- Author
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Scatter plots of HPV 16-L1 methylation in cervical brush (S7a) and urine ccfDNA (S7b). HPV16-L1 qMSP methylation can discriminate bisulfite treated cervical epithelium DNA and urine ccfDNA from patients with normal cytology, from women with dysplastic cytology, and premalignant cervical lesions with high Sensitivity and Specificity.
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- 2023
3. Supplementary Figure 2 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Data Integration modules and systems interface.s
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- 2023
4. Supplementary Figure 2A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
GenoScape - HPV genotype profiling from high-throughput sequencing samples consists of four analytic steps: (1) High-throughput sequencing (454, MiSeq) of HPV TrDNA; (2) Profiling by comparing sequences against several databases such as Human genome (bowtie), HPV databases -GenBank, PaVE, Enterix-HPV Hi-lo risk (sim4db) and RefSeq bacterial genomes (blast); (3) Assembly into contigs, for AlignScape visualization (newbler,minimus, trinity); and SNP discovery (samtools + filter).
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- 2023
5. Supplementary Table 5 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Circulating cell free DNA isolation results.
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- 2023
6. Supplementary Table 8 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Primer and probe list of genes used for quantitative Methylation Specific PCR in urine ccfDNA.
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- 2023
7. Supplementary Table 4 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Mapping efficiency of cervical cancer cell lines, head and neck squamous cell carcinoma cell lines and clinical samples to HPV16-L1.
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- 2023
8. Supplementary Table 2 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Mutational profile in Black HNSCC patients by anatomic site
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- 2023
9. Supplementary Table 2A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Dual Sequence capture of high risk HPV in TrDNA aligned to all high risk HPV types and low risk HPV types from PaVE database.
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- 2023
10. Supplementary Figure 5B from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
AlignScape - Pairwise alignment of the HPV16 genome with reads obtained from urine ccfDNA from seven clinical samples: TrDNA-445, TrDNA-455, TrDNA-456, TrDNA-481, TrDNA-504, TrDNA-513, and TrDNA-571. The large-scale HPV DNA server can produce a graphical 'large-scale' view of the pairwise alignments of up to twenty HPV genomes against a reference genome (HPV16 in this demo), together with annotations of genome rearrangement events.
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- 2023
11. Supplementary Table 1 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
- Author
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Patient characteristics.
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- 2023
12. Supplementary Table 1 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Differences in the frequency of somatic mutations observed in Non-Latino Whites and Black HNSCC patients.
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- 2023
13. Supplementary Table 3 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Reads of the HPV positive cervical cancer, head and neck cancer squamous cell carcinoma (HNSCC) cell lines and clinical samples that mapped uniquely to the reference genomes in the PAVE database.
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- 2023
14. Supplemental Experimental Procedures from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Supplementary Methods.
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- 2023
15. Supplementary Table 3 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
The top differentially altered pathways revealed by Gene Ontology (GO) clustering when comparing Black and NLW HNSCC patients.
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- 2023
16. Supplementary Figure 1B from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Phase 1 Biomarker Development Trial to identify genes or clusters of genes that appear to be differentially methylated in cervical cancer biopsy tissues relative to control cervical brush epithelium tissue taken from women seen in the same hospital. The search for cervical cancer screening methylation biomarkers began with preclinical exploratory studies to identify characteristics unique to tumor tissue that might lead to methylated biomarkers for clinical tests that can discriminate cancer from pre-malignant and normal lesions. We used Methylated DNA Immunoprecipitation (MeDIP) and oligonucleotide sequencing arrays (Nimblegen 385K CpG Island Plus Promoter Arrays) to unveil the cervical cancer promoter region methylome (MeDIP-chip). We then used bisulfite sequencing and quantitative Methylation Specific Polymerase Chain Reaction (qMSP) to identify potential biomarkers of progression from normal cervical mucosa epithelium in cervical brush samples from women with abnormal cytology. MeDIP-chip Discovery identified 2,044 differentially methylated probes associated to total of 444 gene loci differentially methylated when comparing tumor and normal samples. Gene loci were subdivided according to two cutoffs defined for the maximal distance between a methylation peak and the TSS: -1000 to +1000, called the standard cut-off; -500 to +500, called the narrow cut-off. We found 255 unique gene loci that are cancer specific methylated according to the standard cutoff and 189 according to the narrow cutoff. More than half of the methylated gene promoters identified with MeDIP-chip (60%) were hypermethylated in all cancer samples and not in normal samples. One hundred and sixty two (162) genes were jointly identified by the intersection between both lists. These stringent criteria ensured that all 10 genes selected for biomarker validation had methylated peaks within a CPG island located in the promoter region, 500 base pairs upstream from the TSS in all the hybridized tumor samples and none in the normal samples hybridized to the arrays. The top three genes in the list that contained CpG islands in their promoter regions FKBP6, ZNF516 and INTS1) were selected for further analysis with MSP and qMSP in Validation and Prevalence cohorts. Samples were tsted for HPV presence using the reverse line blot assay.
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- 2023
17. Supplementary Table 6 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Goals and Primary Aims of the five phases of the National Cancer Institue Early Detection Research Network biomarker development trials.
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- 2023
18. Supplementary Figure 3A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Amplification curves for the HPV TrDNA-qPCR assay on TrDNA from women with Cervical Intraepithelial Neoplasia 1 (CIN1), Cervical Intraepithelial Neoplasia 2-3 (CIN2-3) and women with no Intraepithelial Lesions or Neoplasia (NILM). TrDNA samples were analyzed for high risk HPV DNA using our HPV TrDNA SYBR green qPCR assay. HeLa genomic DNA was included as a positive control. Ct ranges are variable, but are in a similar range as the genomic control. NILM samples did not amplify.
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- 2023
19. Supplementary Figure 1 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Patient cohorts analyzed in this project.
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- 2023
20. Supplementary Figure 3 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Aircraft Tracking Analogy that integrates Contextual, Bio-psychosocial and Molecular Determinants of Population Health in a Patient Centered Trajectory that can be used in Personalized Medicine workflows.
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- 2023
21. Supplemental Experimental Procedures from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Supplemental Methods, Figures and Tables
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- 2023
22. Data from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Clinically useful molecular tools to triage women for a biopsy upon referral to colposcopy are not available. We aimed to develop a molecular panel to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher lesions (CIN2+) in women with abnormal cervical cytology and high-risk HPV (HPV+). We tested a biomarker panel in cervical epithelium DNA obtained from 211 women evaluated in a cervical cancer clinic in Chile from 2006 to 2008. Results were verified in a prospective cohort of 107 women evaluated in a high-risk clinic in Puerto Rico from 2013 to 2015. Promoter methylation of ZNF516, FKBP6, and INTS1 discriminated cervical brush samples with CIN2+ lesions from samples with no intraepithelial lesions or malignancy (NILM) with 90% sensitivity, 88.9% specificity, 0.94 area under the curve (AUC), 93.1% positive predictive value (PPV), and 84.2% negative predictive value (NPV). The panel results were verified in liquid-based cervical cytology samples from an independent cohort with 90.9% sensitivity, 60.9% specificity, 0.90 AUC, 52.6% PPV, and 93.3% NPV, after adding HPV16-L1 methylation to the panel. Next-generation sequencing results in HPV+ cultured cells, and urine circulating cell-free DNA (ccfDNA) were used to design assays that show clinical feasibility in a subset (n = 40) of paired plasma (AUC = 0.81) and urine (AUC = 0.86) ccfDNA samples obtained from the prospective cohort. Viral and host DNA methylation panels can be tested in liquid cytology and urine ccfDNA from women referred to colposcopy, to triage CIN2+ lesions for biopsy and inform personalized screening algorithms. Cancer Prev Res; 9(12); 915–24. ©2016 AACR.
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- 2023
23. Supplementary Table 4 from JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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David Sidransky, James R. Eshleman, Young J. Kim, William H. Westra, Wayne M. Koch, Luigi Marchionni, Adriana Baez, Oluwasina Folawiyo, Bianca Rivera, Tal Hadar, Blanca L. Valle, Laura Manuel, Francesca Pirini, Maartje G. Noordhuis, Sebastian Rodriguez-Torres, Fahcina Lawson, and Rafael Guerrero-Preston
- Abstract
Cox regression analysis of TCGA Head and Neck Squamous Cell Carcinoma patients (n=279).
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- 2023
24. Supplementary Table 7 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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David Sidransky, Liliana Florea, Bruce J. Trock, Josefina Romaguera, Keimari Méndez, José Rodríguez Orengo, Teresa Diaz-Montes, Edgar De Jesus Rodríguez, Carolina Guerrero-Diaz, Marisa Renehan, Gabriela Pérez, Amanda Dziedzic, Maartje Noordhuis, Angelo Vergura, Fahcina Lawson, Francesca Pirini, Oluwasina Folawiyo, Nitesh Turaga, Anne Jedlicka, Blanca L. Valle, and Rafael Guerrero-Preston
- Abstract
Primer and probe list of genes used for quantitative Methylation Specific PCR.
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- 2023
25. JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients
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Rafael Guerrero-Preston, James R. Eshleman, Oluwasina Folawiyo, Tal Hadar, Young J. Kim, William H. Westra, Maartje G. Noordhuis, Adriana Baez, David Sidransky, Bianca Rivera, Sebastian Rodriguez-Torres, Fahcina Lawson, Luigi Marchionni, Blanca L. Valle, Wayne M. Koch, Laura S. Manuel, and Francesca Pirini
- Subjects
0301 basic medicine ,Oncology ,HUMAN-PAPILLOMAVIRUS HPV ,Cancer Research ,medicine.medical_specialty ,POSITIVE HEAD ,Germline ,RACIAL/ETHNIC DISPARITIES ,AFRICAN-AMERICAN ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Breast cancer ,LUNG-CANCER ,Internal medicine ,Medicine ,BREAST-CANCER ,Lung cancer ,Survival rate ,GENE-EXPRESSION ,business.industry ,Proportional hazards model ,Head and neck cancer ,SOMATIC MUTATIONS ,EPIGENETIC INACTIVATION ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,SQUAMOUS-CELL CARCINOMA ,business - Abstract
To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 (P = 0.06) and PAX1 (P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor–node–metastasis stage (n = 118). We also found that promoter methylation of PAX1 and PAX5 (n = 78), was correlated with neighborhood characteristics at the zip-code level (P < 0.05). Analyses also showed differences in the frequency of TP53 mutations (n = 32) and tumor-infiltrating lymphocyte (TIL) counts (n = 24), and the presence of a specific C → A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n = 73; P < 0.05), when compared with NLW (n = 37) patients. TIL counts are associated (P = 0.035) with long-term (>5 years), when compared with short-term survival (
- Published
- 2019
26. Network Pharmacology and Component Analysis Integrated Study to Unveil Molecular Mechanisms of A Traditional Chinese Medicine Decoction (Polygonum Multiflorum, Rehmannia Glutinosa, Senna Obtusifolia and Crataegus) in Hypertension Treatment
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Fahcina Lawson, Thau Lym Wilson Yong, Fernandes Opook, Fui Fui Lem, and Fong Tyng Chee
- Subjects
Polygonum ,biology ,Traditional medicine ,Hypertension treatment ,Network pharmacology ,Decoction ,Traditional Chinese medicine ,biology.organism_classification ,Rehmannia glutinosa ,Senna obtusifolia ,Crataegus - Abstract
Background: Traditional Chinese Medicines (TCM) are known for their curative effects on hypertension through a holistic approach. The molecular mechanisms of the formulation comprising Polygonum multiflorum, Rehmannia glutinosa, Senna obtusifolia and Crataegus, used by Chinese practitioners in ameliorating hypertension, however remain a mystery. This initial study is thus aimed at unveiling the molecular mechanisms of this TCM formulation in treating hypertension. Methods: The methanolic extract compounds of the decoction were identified through Liquid chromatography mass spectrometry-mass spectrometry (LC-MS/MS). Oral bioavailability and drug likeness were then measured to filter out identified compounds. Several databases, such as the SwissTargetPrediction, STRING, OMIM and KEGG, were used to retrieve information on the predicted targets for the purpose of developing a network using Cytoscape Version 3.8. Enrichment analysis was then performed to elucidate the mechanisms of the decoction in hypertension mitigation. Results: A total of 11 compounds identified were revealed to possess bioavailable and drug like characteristics, based on the Veber and Quantitative Estimation of Drug-likeness (QED) parameters. Pathway analysis showed enrichment of pathways such as cardiac muscle contraction, fluid shear stress and atherosclerosis, dilated cardiomyopathy, renin-angiotensin system and hypertrophic cardiomyopathy (HCM), which are all strongly associated with hypertension. Conclusion: The network pharmacology analysis clearly shows that this TCM decoction ameliorates hypertension through several indirect pathways where most of the targets are involved in HCM, which is caused by hypertension.
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- 2020
27. HIST1H2BB and MAGI2 methylation and somatic mutations as precision medicine biomarkers for diagnosis and prognosis of high-grade serous ovarian cancer
- Author
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Ie Ming Shih, Oluwasina Folawiyo, Fahcina Lawson, Elisabetta Kuhn, Sebastian Rodriguez-Torres, David Sidransky, James G. Herman, Teresa Diaz-Montes, Rafael Guerrero-Preston, Priscilla Brebi-Mieville, Blanca L. Valle, Edgardo Parrilla-Castellar, Carmen Ili-Gangas, and James R. Eshleman
- Subjects
0301 basic medicine ,Cancer Research ,business.industry ,Serous carcinoma ,Bisulfite sequencing ,Methylation ,medicine.disease ,medicine.disease_cause ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Germline mutation ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Biomarker (medicine) ,Medicine ,business ,Carcinogenesis ,Clonogenic assay ,Exome sequencing - Abstract
Molecular alterations that contribute to long-term (LT) and short-term (ST) survival in ovarian high-grade serous carcinoma (HGSC) may be used as precision medicine biomarkers. DNA promoter methylation is an early event in tumorigenesis, which can be detected in blood and urine, making it a feasible companion biomarker to somatic mutations for early detection and targeted treatment workflows. We compared the methylation profile in 12 HGSC tissue samples to 30 fallopian tube epithelium samples, using the Infinium Human Methylation 450K Array. We also used 450K methylation arrays to compare methylation among HGSCs long-term survivors (more than 5 years) and short-term survivors (less than 3 years). We verified the array results using bisulfite sequencing and methylation-specific PCR (qMSP). in another cohort of HGSC patient samples (n = 35). Immunoblot and clonogenic assays after pharmacologic unmasking show that HIST1H2BB and MAGI2 promoter methylation downregulates mRNA expression levels in ovarian cancer cells. We then used qMSP in paired tissue, ascites, plasma/serum, vaginal swabs, and urine from a third cohort of patients with HGSC cancer (n = 85) to test the clinical potential of HIST1H2BB and MAGI2 in precision medicine workflows. We also performed next-generation exome sequencing of 50 frequently mutated in human cancer genes, using the Ion AmpliSeqCancer Hotspot Panel, to show that the somatic mutation profile found in tissue and plasma can be quantified in paired urine samples from patients with HGSC. Our results suggest that HIST1H2BB and MAGI2 have growth-suppressing roles and can be used as HGSC precision medicine biomarkers.
- Published
- 2020
28. Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: A systematic scoping review
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Fong Tyng Chee, Fui Fui Lem, Su Na Chin, Fernandes Opook, Fahcina Lawson, and Dexter Jiunn Herng Lee
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Drug ,Oseltamivir ,COVID-19 ,alternative medicine ,molecular mechanism ,repurposed drugs ,SARS-CoV-2 ,media_common.quotation_subject ,Traditional Chinese medicine ,Pharmacology ,Favipiravir ,Bioinformatics ,chemistry.chemical_compound ,medicine ,Pharmacology (medical) ,media_common ,business.industry ,lcsh:RM1-950 ,Lopinavir ,Clinical trial ,Drug repositioning ,lcsh:Therapeutics. Pharmacology ,chemistry ,Ritonavir ,Systematic Review ,business ,medicine.drug - Abstract
BackgroundThe emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the outbreak. Because of the time constraints associated with the development of vaccines and effective drugs, drug repurposing and other alternative treatment methods have been used to treat patients that have been infected by the SARS-CoV-2 virus and have acquired COVID-19.ObjectiveThe objective of this systematic scoping review is to provide an overview of the molecular mechanism of action of repurposed drugs or alternative treatment medicines used to attenuate COVID-19 disease.Data SourcesThe research articles or grey literature, including theses, government reports, and official news online, were identified from 4 databases and 1 search engine. The full content of a total of 160 articles that fulfilled our inclusion criteria was analyzed and information about 6 drugs (ritonavir, lopinavir, oseltamivir, remdesivir, favipiravir, and chloroquine) and 4 traditional Chinese medicines (Shuang Huang Lian Kou Fu Ye, TCM combination of Bu Huan Jin Zheng Qi San and Da Yuan Yin, Xue Bi Jing Injection and Qing Fei Pai Du Tang) were extracted.ConclusionsAll of the repurposed drugs that have been used for the treatment of COVID-19 depend on the ability of the drug to inhibit the proliferation of the SARS-CoV-2 virus by binding to enzyme active sites, viral chain termination, or triggering of the molecular pathway, whereas traditional Chinese medicine has a pivotal role in triggering the inflammation pathway, such as the neuraminidase blocker, to fight the SARS-CoV-2 virus. This review provides an insight to experimental validation of drugs and alternative medicine used for the treatment and control of COVID-19.
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- 2020
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29. Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
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Teresa P. Díaz-Montes, Maartje G. Noordhuis, Angelo Vergura, Francesca Pirini, David Sidransky, Bruce J. Trock, José F. Rodríguez Orengo, Oluwasina Folawiyo, Liliana Florea, Marisa Renehan, Edgar De Jesus Rodriguez, Rafael Guerrero-Preston, Keimari Mendez, Fahcina Lawson, Josefina Romaguera, Blanca L. Valle, Amanda Dziedzic, Gabriela Perez, Carolina Guerrero-Diaz, Anne E. Jedlicka, and Nitesh Turaga
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0301 basic medicine ,Cancer Research ,Pathology ,Biopsy ,Uterine Cervical Neoplasms ,Gastroenterology ,Human Papillomavirus DNA Tests ,Cohort Studies ,0302 clinical medicine ,Cytology ,Prospective Studies ,NUCLEIC-ACIDS ,Prospective cohort study ,Human Papillomavirus DNA Test ,POPULATION ,Aged, 80 and over ,RISK ,Cervical cancer ,Colposcopy ,Human papillomavirus 16 ,education.field_of_study ,Intraepithelial neoplasia ,medicine.diagnostic_test ,Middle Aged ,CANCER ,DNA-Binding Proteins ,GENOME ,Oncology ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Population ,Wnt1 Protein ,Cervical intraepithelial neoplasia ,Sensitivity and Specificity ,Tacrolimus Binding Proteins ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Vaccines, Virus-Like Particle ,education ,Aged ,Retrospective Studies ,Vaginal Smears ,business.industry ,Papillomavirus Infections ,DNA Methylation ,TRANSRENAL DNA ,PERFORMANCE ,Uterine Cervical Dysplasia ,medicine.disease ,PREVENTION ,030104 developmental biology ,INTRAEPITHELIAL NEOPLASIA ,DNA, Viral ,business ,HPV POSITIVE WOMEN - Abstract
Clinically useful molecular tools to triage women for a biopsy upon referral to colposcopy are not available. We aimed to develop a molecular panel to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher lesions (CIN2+) in women with abnormal cervical cytology and high-risk HPV (HPV+). We tested a biomarker panel in cervical epithelium DNA obtained from 211 women evaluated in a cervical cancer clinic in Chile from 2006 to 2008. Results were verified in a prospective cohort of 107 women evaluated in a high-risk clinic in Puerto Rico from 2013 to 2015. Promoter methylation of ZNF516, FKBP6, and INTS1 discriminated cervical brush samples with CIN2+ lesions from samples with no intraepithelial lesions or malignancy (NILM) with 90% sensitivity, 88.9% specificity, 0.94 area under the curve (AUC), 93.1% positive predictive value (PPV), and 84.2% negative predictive value (NPV). The panel results were verified in liquid-based cervical cytology samples from an independent cohort with 90.9% sensitivity, 60.9% specificity, 0.90 AUC, 52.6% PPV, and 93.3% NPV, after adding HPV16-L1 methylation to the panel. Next-generation sequencing results in HPV+ cultured cells, and urine circulating cell-free DNA (ccfDNA) were used to design assays that show clinical feasibility in a subset (n = 40) of paired plasma (AUC = 0.81) and urine (AUC = 0.86) ccfDNA samples obtained from the prospective cohort. Viral and host DNA methylation panels can be tested in liquid cytology and urine ccfDNA from women referred to colposcopy, to triage CIN2+ lesions for biopsy and inform personalized screening algorithms. Cancer Prev Res; 9(12); 915–24. ©2016 AACR.
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- 2016
30. Abstract A1-50: Genomic and epigenomic alterations in human and high-risk HPV DNA can discriminate normal from cervical dysplasia patients in urine
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Teresa P. Díaz-Montes, Rafael Guerrero-Preston, Oluwasina Folawiyo, Blanca L. Valle, Gabriela T. Pérez, Liliana Florea, Carolina Guerrero-Díaz, Angelo Vergura, Marisa Renehan, David Sidransky, Francesca Pirini, Anne E. Jedlicka, Josefina Romaguera, and Fahcina Lawson
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Oncology ,Colposcopy ,Cervical cancer ,Cancer Research ,medicine.medical_specialty ,Pathology ,medicine.diagnostic_test ,business.industry ,Bisulfite sequencing ,Cancer ,medicine.disease ,Cervical intraepithelial neoplasia ,Dysplasia ,Internal medicine ,Cytology ,DNA methylation ,medicine ,business - Abstract
Human Papilloma Virus (HPV) testing is increasingly used for cervical cancer screening in conjunction with cervical cytology. Although privacy, cultural, and infrastructure issues challenge the effective implementation of HPV testing for cervical cancer screening worldwide, several countries have already implemented HPV testing in their screening protocols. There are currently no tests that can reliably identify the patients with abnormal cytology and positive oncogenic HPV results (HPV+) that need to be referred for colposcopy. A useful triage test from cytology to colposcopy must discriminate the patients with a Cervical Intraepithelial Neoplasia (CIN) lesion that are more likely to progress to cervical cancer (CIN2+), from those that are less likely to progress. We set out to identify a panel of methylated HPV and human genes that can discriminate between CIN2+ and normal/CIN1 patients, first in cytology samples and then in urine samples. The Reverse Line Blot Assay identified high-risk HPV types in study participants from a Discovery cohort (n=96): 31 women with normal cervical cytology and 65 women with dysplasia (LSIL, n=43) and (HSIL, n=22). We developed custom sequence capture pools of baits to pull down genomic (Roche SeqCap EZ) and bisulfite converted high-risk HPV DNA (Agilent SureSelect) from urine, before library prep for NGS in a Roche 454 and MiSeq instruments, respectively. We also optimzed a qPCR assay to identify high risk HPV types, and quantitative Methylation Specific PCR (qMSP) assays to examine methylated HPV and human genes, in Pap smear DNA and TrDNA samples from women with normal Pap and women with CIN1, CIN2 and CIN3 lesions (n=80). The human genes selected for the qMSP assays, ZNF516, FKBP6, and INTS1, were identified in a previously published genome-wide analysis of the cevical cancer methylome using Nimblegen 385K CpG plus Promoters oligonucleotide tiling arrays. Presence of high-risk HPV in cervical epithelium correctly classified 37% of HSIL when compared with LSIL patients, with 61% sensitivity and 22% specificity. Promoter methylation of INTS1 correctly classified 67% (31% sensitivity, 92% specificity), promoter methylation of ZNF516 correctly classified 54% (11% sensitivity, 84% specificity), promoter methylation of FKBP6 correctly classified 59% (19% sensitivity, 88% specificity), and methylation of the HPVL1 gene correctly classified 61% (22% sensitivity, 90% specificity) of HSIL patients when compared with LSIL patients. A molecular panel comprised of HPV16-L1 methylation and promoter methylation of INTS1, ZNF516 and FKBP6 correctly classified 70% of HSIL patients with an Area Under the Curve of 0.66, 44% sensitivity, 88% specificity and 72% Positive Predictive value. While HPV16-L1 methylation discriminated patients with normal cytology from women with cervical dysplasia with close to 100% sensitivity and specificity, the high-risk HPV TrDNA qPCR assay had a pre-capture and post-capture sensitivity of 79% with 50% specificity. The detection of circulating HPV DNA in urine is a cost-effective and non-invasive alternative for cervical cancer screening. We have shown that a panel of genomic and epigenomic alterations in human and high risk HPV DNA can discriminate normal from cervical dysplasia in cervical epithelium DNA and TrDNA isolated from patients seen in a high risk cervical cancer screening setting. Citation Format: Rafael Guerrero-Preston, Anne Jedlicka, Oluwasina Folawiyo, Francesca Pirini, Blanca L. Valle, Fahcina Lawson, Angelo Vergura, Gabriela Perez, Marisa Renehan, Carolina Guerrero-Díaz, Liliana Florea, Teresa Díaz-Montes, Josefina Romaguera, David Sidransky. Genomic and epigenomic alterations in human and high-risk HPV DNA can discriminate normal from cervical dysplasia patients in urine. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-50.
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- 2015
31. INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program
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María Orera-Clemente, Rafael Guerrero-Preston, David Sidransky, Bola Grace Ayandibu, Francesca Pirini, Sebastian Rodriguez-Torres, Alberto Gonzalez-De La Vega, Roland J. Thorpe, and Fahcina Lawson
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global DNA methylation index ,0301 basic medicine ,obesity ,Cancer Research ,G-protein subunit β3 ,Bioinformatics ,Biochemistry ,apolipoprotein A5 ,Gene Frequency ,near insulin-induced gene 2 ,Weight loss ,lipid metabolism ,single nucleotide variant ,adrenoceptor β2 ,Child ,2. Zero hunger ,INSIG2 ,Intracellular Signaling Peptides and Proteins ,Articles ,Middle Aged ,3. Good health ,Melanocortin 4 receptor ,Weight Reduction Programs ,Treatment Outcome ,Oncology ,DNA methylation ,Molecular Medicine ,medicine.symptom ,Adult ,Adolescent ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Young Adult ,Weight Loss ,Genetics ,medicine ,Humans ,personalized weight reduction program ,Obesity ,Allele ,Molecular Biology ,Genetic Association Studies ,Aged ,Membrane Proteins ,DNA Methylation ,medicine.disease ,energy balance ,melanocortin 4 receptor ,030104 developmental biology ,Body mass index - Abstract
Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet‑induced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a non‑surgical weight loss regimen. The present study included 105 obese participants that were enrolled in a personalized weight loss program based on their allelic composition of the following five energy balance and lipid metabolism‑associated loci: Near insulin‑induced gene 2 (INSIG2); melanocortin 4 receptor; adrenoceptor β2; apolipoprotein A5; and G‑protein subunit β3. The present study investigated the association between a global DNA methylation index (GDMI), the allelic composition of the five energy balance and lipid metabolism‑associated loci, and weight loss during a 12 month program, after controlling for age, sex and body mass index (BMI). The results demonstrated a significant association between the GDMI and near INSIG2 locus, after adjusting for BMI and weight loss, and significant trends were observed when stratifying by gender. In conclusion, a combination of genetic and epigenetic biomarkers may be used to design personalized weight loss interventions, enabling adherence and ensuring improved outcomes for obesity treatment programs. Precision weight loss programs designed based on molecular information may enable the creation of personalized interventions for patients, that use genomic biomarkers for treatment design and for treatment adherence monitoring, thus improving response to treatment.
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- 2018
32. Nuclear and Mitochondrial DNA Alterations in Newborns with Prenatal Exposure to Cigarette Smoke
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Andrea Mancinelli, Fahcina Lawson, Rafael Guerrero-Preston, Elisa Guida, and Francesca Pirini
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Mitochondrial DNA ,Health, Toxicology and Mutagenesis ,Respiratory chain ,lcsh:Medicine ,Physiology ,Review ,mitochondrial DNA ,molecular biomarkers ,Pregnancy ,environmental cigarette smoke effects ,Genetic predisposition ,medicine ,Humans ,Epigenetics ,Genetics ,Fetus ,epigenomics effects ,DNA methylation ,business.industry ,Smoking ,lcsh:R ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,maternal cigarette smoke effects ,DNA ,in utero exposures ,medicine.disease ,3. Good health ,Nuclear DNA ,In utero ,Female ,business ,DNA Damage - Abstract
Newborns exposed to maternal cigarette smoke (CS) in utero have an increased risk of developing chronic diseases, cancer, and acquiring decreased cognitive function in adulthood. Although the literature reports many deleterious effects associated with maternal cigarette smoking on the fetus, the molecular alterations and mechanisms of action are not yet clear. Smoking may act directly on nuclear DNA by inducing mutations or epigenetic modifications. Recent studies also indicate that smoking may act on mitochondrial DNA by inducing a change in the number of copies to make up for the damage caused by smoking on the respiratory chain and lack of energy. In addition, individual genetic susceptibility plays a significant role in determining the effects of smoking during development. Furthermore, prior exposure of paternal and maternal gametes to cigarette smoke may affect the health of the developing individual, not only the in utero exposure. This review examines the genetic and epigenetic alterations in nuclear and mitochondrial DNA associated with smoke exposure during the most sensitive periods of development (prior to conception, prenatal and early postnatal) and assesses how such changes may have consequences for both fetal growth and development.
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- 2015
33. 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment
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William H. Westra, Oluwasina Folawiyo, Rajagowthamee R. Thangavel, A. Rodriguez, Tal Hadar, Fahcina Lawson, Maartje G. Noordhuis, Wayne M. Koch, Filipa Godoy-Vitorino, Jessica Bondy, Anne E. Jedlicka, David Sidransky, M. Michailidi, Amanda Dziedzic, Herminio González, and Rafael Guerrero-Preston
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0301 basic medicine ,Male ,oropharyngeal cancer ,Oral Surgical Procedures ,microbiome ,Toxicology ,GUT MICROBIOME ,COLORECTAL-CANCER ,Cohort Studies ,fluids and secretions ,Risk Factors ,RNA, Ribosomal, 16S ,Medicine ,Longitudinal Studies ,Papillomaviridae ,Surgical treatment ,NEISSERIA-LACTAMICA ,16s rRNA ,Mouth neoplasm ,biology ,Microbiota ,human papilloma virus (HPV) ,BACTERIA PRESENT ,General Medicine ,Middle Aged ,Prognosis ,humanities ,PANCREATIC-CANCER ,3. Good health ,Oncology ,Head and Neck Neoplasms ,Amplicon sequencing ,Carcinoma, Squamous Cell ,Dialister ,Female ,Mouth Neoplasms ,SQUAMOUS-CELL CARCINOMA ,Research Paper ,medicine.medical_specialty ,Aggregatibacter ,Microbiology ,03 medical and health sciences ,stomatognathic system ,HELICOBACTER-PYLORI ,Internal medicine ,Humans ,Human papilloma virus infection ,Microbiome ,HEAD ,Oral Cavity Squamous Cell Carcinoma ,NECK ,Aged ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Papillomavirus Infections ,Gene Amplification ,Cancer ,Fusobacteria ,oral cancer ,16S ribosomal RNA ,biology.organism_classification ,medicine.disease ,Virology ,Head and neck squamous-cell carcinoma ,stomatognathic diseases ,030104 developmental biology ,SUBGINGIVAL PLAQUE ,business - Abstract
// Rafael Guerrero-Preston 1, 2 , Filipa Godoy-Vitorino 3 , Anne Jedlicka 4 , Arnold Rodriguez-Hilario 3 , Herminio Gonzalez 3 , Jessica Bondy 1 , Fahcina Lawson 1 , Oluwasina Folawiyo 1 , Christina Michailidi 1 , Amanda Dziedzic 4 , Rajagowthamee Thangavel 5 , Tal Hadar 1 , Maartje G. Noordhuis 1, 6 , William Westra 7 , Wayne Koch 1 , David Sidransky 1 1 Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2 Department of Obstetrics and Gynecology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 3 Natural Sciences Department, Microbial Ecology and Genomics Laboratory, Inter American University of Puerto Rico, Metropolitan Campus, San Juan, Puerto Rico 4 Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA 6 Department of Otorhinolaryngology-Head and Neck Surgery, University of Groningen, University Medical Center, Groningen, The Netherlands 7 Department of Pathology-Surgical Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to: Rafael Guerrero-Preston, email: rguerre3@jhmi.edu David Sidransky, email: dsidrans@jhmi.edu Keywords: microbiome, 16s rRNA, oral cancer, oropharyngeal cancer, human papilloma virus (HPV) Received: February 23, 2016 Accepted: May 16, 2016 Published: May 30, 2016 ABSTRACT Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection. The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella , with lower numbers of Citrobacter and Neisseraceae genus Kingella . HNSCC patients had a significant loss in richness and diversity of microbiota species (p
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- 2016
34. Abstract B43: Germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health differ in Black and non-Latino White head and neck cancer patients
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Adriana Baez Bermejo, Luigi Marchionni, Tal Hadar, Rafael Guerrero-Preston, Fahcina Lawson, William H. Westra, Blanca L. Valle, David Sidransky, Laura S. Manuel, Wayne M. Koch, Bianca Rivera, and Oluwasina Folawiyo
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Genetics ,Epidemiology ,Somatic cell ,Head and neck cancer ,Cancer ,Biology ,medicine.disease ,Head and neck squamous-cell carcinoma ,Germline ,Germline mutation ,Oncology ,DNA methylation ,medicine ,Epigenetics - Abstract
Somatic mutations play an important role in cancer prognosis and can pave the way for precision medicine to overcome cancer disparities. Current models hold that solid tumors evolve from microscopic clonal cellular proliferations driven through progressive histologic stages by the acquisition of somatic alterations. The accumulation of somatic mutations is associated to varying rates of stem cell divisions, leading to replicative errors that arise in response to hereditary burden, environmental stressors, or random error. Environmental, lifestyle, and neighborhood factors track closely with the acquisition of DNA methylation alterations and may partly explain the differential accumulation of genetic alterations in cancer patients. However, the combined roles of germline and somatic mutation burden, promoter methylation, and neighborhood characteristics in cancer disparities are unknown, in large part because most of the genomic studies have been performed on genomes of European descendants. Here we show that neighborhood characteristics linked to genetic, epigenetic, and tumor-associated immune signatures differ in Black and non-Latino White (NLW) head and neck squamous cell carcinoma (HNSCC) patients. Promoter methylation in PAX genes is associated to neighborhood characteristics at the zip code level (p A germline mutation in JAK3, chr19:17954215 (protein P132T), differ in Black when compared to NLW HNSCC patients (p Citation Format: Rafael Guerrero-Preston, Fahcina Lawson, Laura Manuel, Blanca Valle, Tal Hadar, Bianca Rivera, Oluwasina Folawiyo, Adriana Baez Bermejo, Luigi Marchionni, Wayne Koch, William Westra, David Sidransky. Germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health differ in Black and non-Latino White head and neck cancer patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B43.
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- 2018
35. Abstract B52: Promoter methylation, stage at presentation, and neighborhood-level effects are linked to survival disparities in HNSCC patients
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Rafael Guerrero-Preston, David Sidransky, Francesca Pirini, Fahcina Lawson, Blanca L. Valle, Nitesh Turaga, and Oluwasina Folawiyo
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Oncology ,Gerontology ,medicine.medical_specialty ,Multivariate analysis ,Epidemiology ,business.industry ,Head and neck cancer ,HPV infection ,Cancer ,Disease ,medicine.disease ,Head and neck squamous-cell carcinoma ,Health equity ,Internal medicine ,medicine ,Population study ,business - Abstract
Introduction: Head and neck squamous cell carcinoma (HNSCC) survival has steadily increased over the last 50 years, but the survival gap between African Americans (AAs) and Non-Latino Whites (NLWs) has remained practically unchanged. Most of the survival differences in HNSCC survival are due to HPV infection among oropharyngeal patients, which is mostly seen in younger white males and has better prognosis than HPV-negative disease. HPV-negative HNSCC survival among AAs is associated with stage at presentation, treatment compliance, and other health services related factors. Little is known about how molecular and neighborhood-level effects are linked to HNSCC survival. Our objective is to determine the extent to which molecular alterations; clinical factors and neighborhood-level interactions are linked with HNSCC survival. We hypothesize that HNSCC survival is associated with promoter methylation and neighborhood zip code level measures of education, income, health insurance and housing variables. Methods: We conducted a retrospective analysis in specimens collected between 1985 and 2010 from the Johns Hopkins Head and Neck Cancer tumor bank. Neighborhood-level characteristics at the zip code level were collected from the US Census Bureau. We estimated HNSCC survival linked to molecular, clinical, and neighborhood variables using the Kaplan-Meier method. The log-rank test was used to test the significance of the association between survival and the following categorical variables: promoter methylation of EDNRB, NID2, PAX5, PAX1 and tumor stage; and the following determinants of health at the zip code level: high school diploma, median family income, health insurance, home ownership rate and home vacancy rate. Cox proportional hazard regression was used to test the significance of the association between survival and the following continuous variables: promoter methylation of EDNRB, NID2, PAX5, PAX1 and the following determinants of health at the zip code level: high school diploma, median family income, health insurance, home ownership rate and home vacancy rate. We then used Cox proportional hazard models for univariate and multivariate analyses. Multiple regression models were developed to describe the relationship between HNSCC survival and differential promoter methylation, clinical factors and neighborhood-level interactions within the entire study population and among racial strata. Analyses were performed using STATA version 13. Results: Of 117 patients, 63 AAs and 56 NLWs, AAs had significantly lower 5-year HNSCC cancer survival rates compared to NLWs (57% versus 67%). Within racial strata, multivariate analysis revealed that at the molecular level promoter methylation of EDNRB, NID2 and PAX5 are significant. At the individual level, tumor stage is a significantly strong predictor of HNSCC survival and has an increased HR for tumors that are at stage I (HR 4.3; 95% CI .94, 20) and II (HR 6.0; 95% CI 1.4, 26). At the neighborhood-level, health insurance, home ownership rate and home vacancy rate displayed an association with survival (P Conclusion: We conclude that HNSCC survival is driven by differences in promoter methylation of EDNRB, NID2 and PAX5 at the molecular-level, tumor stage at the individual-level and neighborhood-level effects such as health insurance, home ownership rate and home vacancy rate. Iterations of this work will improve our understanding of how molecular, individual and neighborhood-level factors influence cancer risk and survival, potentially leading to improved prevention and treatment strategies and the elimination of cancer health disparities. Citation Format: Fahcina P. Lawson, Oluwasina Folawiyo, Blanca L. Valle, Francesca Pirini, Nitesh Turaga, David Sidransky, Rafael E. Guerrero-Preston. Promoter methylation, stage at presentation, and neighborhood-level effects are linked to survival disparities in HNSCC patients. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B52.
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- 2016
36. Abstract B11: Viral and host gene methylation in liquid prep: novel molecular screening and triage tools to reduce cervical cancer disparities
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Carolina Guerrero-Díaz, Francesca Pirini, Oluwasina Folawiyo, Edgardo De Jesus, Teresa P. Díaz-Montes, Maartje G. Noordhuis, Angelo Vergura, Anne E. Jedlicka, Keimari Mendez, Marisa Renehan, Fahcina Lawson, Rafael Guerrero-Preston, Liliana Florea, Nitesh Turaga, Gabriela T. Pérez, David Sidransky, Bruce J. Trock, Josefina Romaguera, and Blanca L. Valle
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Colposcopy ,Gynecology ,Oncology ,Cervical cancer ,medicine.medical_specialty ,medicine.diagnostic_test ,Epidemiology ,business.industry ,Bisulfite sequencing ,Cancer ,medicine.disease ,Molecular diagnostics ,Cervical intraepithelial neoplasia ,Internal medicine ,DNA methylation ,medicine ,Carcinoma ,business - Abstract
Latino women in the United States have the highest cervical cancer incidence rate, yet the highest death rate from cervical cancer is among Black women. The disproportionate burden of cervical cancer in the United States is primarily due to lack of screening, among the medically underserved, regardless of race or ethnicity. Rural and inner city women living in poverty have lower rates of screening and higher rates of cervical cancer in the US. The advent of molecular diagnostics provides an opportunity to develop novel cervical cancer screening and triage tools that can be packaged as point of care and self-testing solutions. We set out to identify a panel of methylated HPV DNA and human genes that can discriminate between CIN2+ and normal/CIN1 patients in liquid prep samples and in Transrenal DNA (TrDNA) isolated from urine. We used three independent cohorts, from Chile, Baltimore and Puerto Rico, to develop a method that can be used to triage into colposcopy, HPV+ women with abnormal cytology. Participants were women with no cervical intraepithelial lesions or malignancy and women with abnormal cervical biopsies– Cervical Intraepithelial Neoplasia (CIN), carcinoma in-situ and cervical cancer. Using DNA methylation arrays for Discovery and quantitative Methylation Specific PCR (qMSP) for Validation, we found that promoter methylation of ZNF516, FKBP6, and INST1 discriminates samples with CIN2+ lesions from samples with no intraepithelial lesions or malignancy (NILM): 88.3% sensitivity, 88.9% specificity, 93.2 Area Under the Curve (AUC), 86.9% positive predictive value (PPV) and 90.2% negative predictive value (NPV). Using custom sequence capture pools of baits, we pulled down genomic and bisulfite converted high-risk HPV DNA before library prep for NGS in 454 and MiSeq instruments, respectively. Using our NGS results, we optimized a Syber Greeen qPCR assay to detect high risk HPV DNA and a qMSP primer-probe set to detect methylated HPV. We replicated the results in liquid prep samples (n=67), adding HPV16 methylation to the panel: 90.9% sensitivity, 60.9% specificity, 90.1 (AUC), 52.6% positive predictive value (PPV) and 93.3% NPV. These results were verified in plasma DNA (AUC=80.7) and TrDNA (AUC=86.1) isolated from a subset of patients who provided the liquid prep samples. Our results suggest that our panel of viral and host gene methylation markers may be used as a reflex test in liquid prep to triage high risk HPV positive women into colposcopy, or as a screening and triage test in TrDNA, in combination with our high risk HPV test. There are several commercial co-testing options for identification of oncogenic high-risk HPV types (HPV+) in patients with abnormal cytology. However, there are currently no tests that can reliably identify the HPV+ patients with abnormal cytology that need to be referred for colposcopy. Consequently, more than half of the women that are referred to colposcopy either have a negative biopsy, or a grade 1 Cervical Intraepithelial Neoplasia (CIN1) diagnosis, which usually reverts to normal in 12-24 months. A triage test from cytology to colposcopy that can identify in the liquid prep sample those patients with a CIN grade more likely to progress to cervical cancer (CIN2+), would decrease the number of unnecessary cervical mucosa biopsies performed today, decreasing health care cost and improving the quality of health care delivery. These molecular tools can also be packaged as point of care and self-testing solutions to eliminate cervical cancer disparities in medically underserved women. Note: This abstract was not presented at the conference. Citation Format: Rafael Guerrero-Preston, Anne Jedlicka, Blanca L. Valle, Nitesh Turaga, Liliana Florea, Oluwasina Folawiyo, Francesca Pirini, Fahcina Lawson, Angelo Vergura, Maartje Noordhuis, Gabriela Perez, Marisa Renehan, Carolina Guerrero-Díaz, Edgardo De Jesus, Teresa Diaz-Montes, Bruce Trock, Keimari Mendez, Josefina Romaguera, David Sidransky. Viral and host gene methylation in liquid prep: novel molecular screening and triage tools to reduce cervical cancer disparities. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B11.
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- 2016
37. Abstract A28: Enrolling African Americans into a cancer-related biobank
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Oluwasina Folawiyo, Francesca Pirini, Blanca L. Valle, Fahcina Lawson, Lori H. Erby, David Sidransky, Jean G. Ford, and Rafael Guerrero-Preston
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Gerontology ,Community engagement ,Family Cancer History ,Epidemiology ,business.industry ,Ethnic group ,Community-based participatory research ,Cancer Biobank ,Focus group ,Biobank ,Health equity ,Oncology ,Medicine ,business - Abstract
Background: Biobanks serve as essential resources for genetic and public health research. Despite their potential utility in elucidation of cancer susceptibility and development of novel cancer surveillance, diagnostic, and therapeutic approaches, most genomic research studies rely on samples with limited ethnic diversity. There is also a suggestion that disparities in participation in cancer biospecimen research have already translated into fewer efficacious treatments for under-represented groups. Inclusion of more diverse populations in biospecimen banks could ultimately contribute to a reduction in disparities in cancer morbidity and mortality that adversely impact U.S. minority groups. Research Objectives: We hypothesized that a deliberative group consent process related to cancer biobank donation would increase African American community engagement, foster an open dialogue between community members and researchers present at the discussion, allow participants to have their concerns addressed, and improve community members' knowledge and attitudes, leading to donation of biospecimens. Methods: We employed a two-stage study design. During the first stage, the Johns Hopkins Center to Reduce Cancer Disparities (JHCRCD) used a Community Based Participatory Research (CBPR) framework that explored the knowledge and attitudes of African American adults in Maryland regarding participation in a cancer biospecimen repository. We completed eight focus groups with primarily African American communities in Baltimore City and Prince George's County. Results: Stage-one results indicate that African American residents of Baltimore and Prince Georges County face limited understanding and lack of awareness in genetics and genomics. Our baseline analyses revealed limited community knowledge about biobanking and initial reluctance to donate biospecimen samples. Some participants expressed distrust in the research enterprise. After some discussion, however, participants were able to identify personal, familial, and societal benefits to participation. Moreover, focus group participants identified a number of strategies to overcome concerns and to enhance participation, including mechanisms for enhanced communication with researchers and suggestions related to building the biobank's community presence. In spite of initial concerns expressed during the focus groups, most participants stated their willingness to donate a specimen in the future if their concerns were properly addressed. Conclusions and Next Steps: Future reductions in cancer morbidity and mortality among minority groups will depend upon increasing the diversity of populations donating samples. The proposed project will provide data to support early communication and transparency to build community trust from the earliest stages of the cancer research process. Stage two of the project will commence in September of 2014. During the second stage, we propose: (a) To examine the impact of a deliberative group consent process on community members' attitudes and knowledge related to donating specimens to a pilot cancer biobank; (b) To identify participant characteristics (including genetic literacy, educational status, gender, personal cancer history, family cancer history, attitudes, and knowledge) that predict actual donation to a pilot cancer biobank; and (c) To create a pilot (small scale) cancer biobank with samples from the African American community for use in future genomic and epigenomic studies Citation Format: Fahcina P. Lawson, Oluwasina Folawiyo, Francesca Pirini, Blanca L. Valle, David Sidransky, Jean Ford, Lori Erby, Rafael Guerrero-Preston. Enrolling African Americans into a cancer-related biobank. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A28.
- Published
- 2015
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