25 results on '"Saxe DF"'
Search Results
2. Biological and biochemical properties of a human uveal melanocyte-derived cell line
- Author
-
Saxe Df, Ray Cg, Frank L. Meyskens, Pacelli Lz, Berglund Eb, Fuller Bb, and Hall Jd
- Subjects
Male ,Plating efficiency ,Cell division ,Adolescent ,Ultraviolet Rays ,Tyrosinase ,Plant Science ,Biology ,Melanocyte ,Cell Line ,medicine ,Ultraviolet light ,Doubling time ,Humans ,Uvea ,Genetics ,Melanins ,Monophenol Monooxygenase ,Molecular biology ,Hormones ,medicine.anatomical_structure ,Cell culture ,Karyotyping ,Viruses ,Melanocytes ,Cell Division ,Biotechnology - Abstract
A human uveal melanocyte-derived cell line (U1I) is described. The cell line has a doubling time of 27.2 hr, a plating efficiency on plastic surfaces of 10%, and a cloning efficiency in soft agar of < 0.1%. U1I displays marked chromosomal aneuploidy and sensitivity to ultraviolet light. Biochemical studies indicate the presence of tyrosinase, which is stimulated by several compounds, including theophylline, progesterone, and nerve growth factor.
- Published
- 1980
3. Copy number assessment in the genomic analysis of CNS neoplasia: An evidence-based review from the cancer genomics consortium (CGC) working group on primary CNS tumors.
- Author
-
Neill SG, Hauenstein J, Li MM, Liu YJ, Luo M, Saxe DF, and Ligon AH
- Subjects
- Central Nervous System Neoplasms genetics, Central Nervous System Neoplasms mortality, Central Nervous System Neoplasms therapy, Clinical Decision-Making, Humans, Patient Selection, Practice Guidelines as Topic, Prognosis, Progression-Free Survival, Risk Assessment methods, Risk Assessment standards, Central Nervous System Neoplasms diagnosis, DNA Copy Number Variations, Genomics standards, Medical Oncology standards
- Abstract
The period from the 1990s to the 2010s has witnessed a burgeoning sea change in the practice of surgical neuropathology due to the incorporation of genomic data into the assessment of a range of central nervous system (CNS) neoplasms. This change has since matured into the adoption of genomic information into the definition of several World Health Organization (WHO)-established diagnostic entities. The data needed to accomplish the modern diagnosis of CNS neoplasia includes DNA copy number aberrations that may be assessed through a variety of mechanisms. Through a review of the relevant literature and professional practice guidelines, here we provide a condensed and scored overview of the most critical DNA copy number aberrations to assess for a selection of primary CNS neoplasms., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
- Full Text
- View/download PDF
4. Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma.
- Author
-
Buchwald ZS, Tian S, Rossi M, Smith GH, Switchenko J, Hauenstein JE, Moreno CS, Press RH, Prabhu RS, Zhong J, Saxe DF, Neill SG, Olson JJ, Crocker IR, Curran WJ, and Shu HG
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, Disease-Free Survival, Female, Genomics methods, Humans, Male, Middle Aged, Multivariate Analysis, Progression-Free Survival, Brain Neoplasms genetics, Brain Neoplasms pathology, DNA Copy Number Variations genetics, Glioblastoma genetics, Glioblastoma pathology, Glioma genetics, Glioma pathology
- Abstract
Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.
- Published
- 2020
- Full Text
- View/download PDF
5. Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy.
- Author
-
Greenwell IB, Staton AD, Lee MJ, Switchenko JM, Saxe DF, Maly JJ, Blum KA, Grover NS, Mathews SP, Gordon MJ, Danilov AV, Epperla N, Fenske TS, Hamadani M, Park SI, Flowers CR, and Cohen JB
- Subjects
- Adult, Aged, Aged, 80 and over, Combined Modality Therapy methods, Female, Follow-Up Studies, Genetic Testing methods, Humans, Karyotype, Karyotyping methods, Ki-67 Antigen analysis, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Predictive Value of Tests, Prognosis, Progression-Free Survival, Retrospective Studies, Risk Assessment methods, Transplantation, Autologous, United States epidemiology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosome Aberrations, Hematopoietic Stem Cell Transplantation, Lymphoma, Mantle-Cell therapy, Remission Induction methods
- Abstract
Background: Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy., Methods: The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL., Results: A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and progression-free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who underwent high-intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P = .02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P = .01]) and Ki-67 >30% (HR, 1.86; 95% CI, 1.06-3.28 [P = .03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival., Conclusions: CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306-15. © 2018 American Cancer Society., (© 2018 American Cancer Society.)
- Published
- 2018
- Full Text
- View/download PDF
6. Genomic Analysis in the Practice of Surgical Neuropathology: The Emory Experience.
- Author
-
Neill SG, Saxe DF, Rossi MR, Schniederjan MJ, and Brat DJ
- Subjects
- Biomarkers, Tumor genetics, Humans, Neurosurgery, Central Nervous System Neoplasms genetics, Gene Expression Profiling methods, Neuropathology methods, Pathology, Surgical methods
- Abstract
The evaluation of central nervous system tumors increasingly relies on molecular genetic methods to aid in classification, offer prognostic information, and predict response to therapy. Available assays make it possible to assess genetic losses, amplifications, translocations, mutations, or the expression levels of specific gene transcripts or proteins. Current molecular diagnostics frequently use a panel-based approach and whole genome analysis, and generally rely either on DNA sequencing or on hybridization-based methodologies, such as those used in cytogenomic microarrays. In some cases, immunohistochemistry can be used as a surrogate for genetic analysis when the mutation of interest consistently results in overexpression or underexpression of a known protein product. In surgical neuropathology practice, the diagnostic workup of diffuse gliomas, medulloblastomas, low-grade circumscribed gliomas, as well as other diseases, now routinely incorporates the results of genomic studies. Here we summarize our institution's current approach to diagnostic surgical neuropathology, using these contemporary molecular diagnostic applications.
- Published
- 2017
- Full Text
- View/download PDF
7. Section E6.5-6.8 of the ACMG technical standards and guidelines: chromosome studies of lymph node and solid tumor-acquired chromosomal abnormalities.
- Author
-
Cooley LD, Morton CC, Sanger WG, Saxe DF, and Mikhail FM
- Subjects
- Bone Marrow pathology, Cytodiagnosis standards, Cytogenetic Analysis standards, Genomics standards, Guidelines as Topic, Humans, Laboratories standards, Neoplasms pathology, United States, Chromosome Aberrations, Genetic Testing standards, Neoplasms diagnosis, Neoplasms genetics
- Abstract
Disclaimer: These ACMG standards and guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these standards and guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Cytogenetic analysis of tumor tissue is performed to detect and characterize chromosomal aberrations to aid histopathological and clinical diagnosis and patient management. At the time of diagnosis, known recurrent clonal aberrations may facilitate histopathological diagnosis and subtyping of the tumor. This information may contribute to clinical therapeutic decisions. However, even when tumors have a known recurrent clonal aberration, each tumor is genetically unique and probably heterogeneous. It is important to discover as much about the genetics of a tumor at diagnosis as is possible with the methods available for study of the tumor material. The information gathered at initial study will inform follow-up studies, whether for residual disease detection, determination of relapse and clonal evolution, or identifying a new disease clone.This updated Section E6.5-6.8 has been incorporated into and supersedes the previous Sections E6.4 and E6.5 in Section E: Clinical Cytogenetics of the 2009 Edition (Revised 01/2010), American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories. This section deals specifically with the standards and guidelines applicable to lymph node and solid tumor chromosome analysis.Genet Med 18 6, 643-648.
- Published
- 2016
- Full Text
- View/download PDF
8. Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies.
- Author
-
Fisher KE, Zhang L, Wang J, Smith GH, Newman S, Schneider TM, Pillai RN, Kudchadkar RR, Owonikoko TK, Ramalingam SS, Lawson DH, Delman KA, El-Rayes BF, Wilson MM, Sullivan HC, Morrison AS, Balci S, Adsay NV, Gal AA, Sica GL, Saxe DF, Mann KP, Hill CE, Khuri FR, and Rossi MR
- Subjects
- ErbB Receptors genetics, Humans, In Situ Hybridization, Fluorescence, Limit of Detection, Multiplex Polymerase Chain Reaction methods, Multiplex Polymerase Chain Reaction standards, Mutation, Paraffin Embedding, Quality Control, Receptor, ErbB-2 genetics, Sensitivity and Specificity, Tumor Suppressor Protein p53 genetics, Carcinoma, Non-Small-Cell Lung genetics, Gastrointestinal Neoplasms genetics, High-Throughput Nucleotide Sequencing methods, Lung Neoplasms genetics, Melanoma genetics
- Abstract
We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
9. Subjectivity in chromosome band-level estimation: a multicenter study.
- Author
-
Geiersbach KB, Gardiner AE, Wilson A, Shetty S, Bruyère H, Zabawski J, Saxe DF, Gaulin R, Williamson C, and Van Dyke DL
- Subjects
- Cytogenetics, Humans, United Kingdom, Amniotic Fluid cytology, Blood Cells cytology, Chromosome Banding methods, Karyotype
- Abstract
Purpose: Chromosome band level is the primary quality indicator for G-banded metaphase chromosome analysis. Although current professional guidelines address the minimum necessary band level for constitutional studies, there is no study documenting the comparative performance of different band-level estimation methods., Methods: This study compared 5 band-level estimation methods (Stallard, Vancouver, Welborn, United Kingdom External Quality Assurance Scheme, and Ford) in a multicenter study in which 82 readers from 7 different clinical cytogenetics laboratories evaluated the same 10 karyotypes (5 from amniotic fluid and 5 from peripheral blood) by each method., Results: There was a 94% correlation between the five band-level estimation methods. The Welborn method yielded significantly lower scores for amniotic fluid karyotypes (P < 0.01) but not for peripheral blood karyotypes (P = 0.75). The distribution of scores obtained from different readers suggests a high level of subjectivity in chromosome band-level assessment. The variation in band-level estimation did not correlate with reader experience or study center, except for readers from one laboratory, for which the distribution of scores was significantly lower (P < 0.01)., Conclusion: The results from this study suggest that the consistent use of one method is more important than the actual method employed for monitoring karyotype quality.
- Published
- 2014
- Full Text
- View/download PDF
10. Validation of fluorescence in situ hybridization using an analyte-specific reagent for detection of abnormalities involving the mixed lineage leukemia gene.
- Author
-
Saxe DF, Persons DL, Wolff DJ, and Theil KS
- Subjects
- Cell Nucleus pathology, Humans, Interphase, Leukemia, Biphenotypic, Acute pathology, Reproducibility of Results, Sensitivity and Specificity, United States, United States Food and Drug Administration, Fluorescent Dyes, In Situ Hybridization, Fluorescence methods, Leukemia, Biphenotypic, Acute diagnosis, Leukemia, Biphenotypic, Acute genetics, Molecular Diagnostic Techniques standards, Myeloid-Lymphoid Leukemia Protein genetics
- Abstract
Context: Fluorescence in situ hybridization (FISH) is a molecular cytogenetic assay that is commonly used in laboratory medicine. Most FISH assays are not approved by the US Food and Drug Administration but instead are laboratory-developed tests that use analyte-specific reagents. Although several guidelines exist for validation of FISH assays, few specific examples of FISH test validations are available in the literature., Objective: To provide an example of how a FISH assay, using an analyte-specific reagent probe, may be validated in a clinical laboratory., Design: We describe the approach used by an individual laboratory for validation of a FISH assay for mixed lineage leukemia (MLL) gene., Results: Specific validation data are provided illustrating how initial assay performance characteristics in a FISH assay for MLL may be established., Conclusions: Protocols for initial validation of FISH assays may vary between laboratories. However, all laboratories must establish several defined performance specifications prior to implementation of FISH assays for clinical use. We describe an approach used for assessing performance specifications and validation of an analyte-specific reagent FISH assay using probes for MLL rearrangement in interphase nuclei.
- Published
- 2012
- Full Text
- View/download PDF
11. College of American Pathologists/American College of Medical Genetics proficiency testing for constitutional cytogenomic microarray analysis.
- Author
-
Brothman AR, Dolan MM, Goodman BK, Park JP, Persons DL, Saxe DF, Tepperberg JH, Tsuchiya KD, Van Dyke DL, Wilson KS, Wolff DJ, and Theil KS
- Subjects
- Cytogenetic Analysis methods, Data Collection, Humans, Laboratories standards, Microarray Analysis methods, Societies, Medical, United States, Cytogenetic Analysis standards, Laboratory Proficiency Testing standards, Microarray Analysis standards
- Abstract
Purpose: To evaluate the feasibility of administering a newly established proficiency test offered through the College of American Pathologists and the American College of Medical Genetics for genomic copy number assessment by microarray analysis, and to determine the reproducibility and concordance among laboratory results from this test., Methods: Surveys were designed through the Cytogenetic Resource Committee of the two colleges to assess the ability of testing laboratories to process DNA samples provided and interpret results. Supplemental questions were asked with each Survey to determine laboratory practice trends., Results: Twelve DNA specimens, representing 2 pilot and 10 Survey challenges, were distributed to as many as 74 different laboratories, yielding 493 individual responses. The mean consensus for matching result interpretations was 95.7%. Responses to supplemental questions indicate that the number of laboratories offering this testing is increasing, methods for analysis and evaluation are becoming standardized, and array platforms used are increasing in probe density., Conclusion: The College of American Pathologists/American College of Medical Genetics proficiency testing program for copy number assessment by cytogenomic microarray is a successful and efficient mechanism for assessing interlaboratory reproducibility. This will provide laboratories the opportunity to evaluate their performance and assure overall accuracy of patient results. The high level of concordance in laboratory responses across all testing platforms by multiple facilities highlights the robustness of this technology.
- Published
- 2011
- Full Text
- View/download PDF
12. NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary.
- Author
-
Shehata BM, Steelman CK, Abramowsky CR, Olson TA, French CA, Saxe DF, Ricketts RR, and Katzenstein HM
- Subjects
- Carcinoma congenital, Carcinoma genetics, Cell Cycle Proteins, Child, Preschool, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 9, Combined Modality Therapy, Fatal Outcome, Humans, Infant, Newborn, Liver Neoplasms congenital, Liver Neoplasms genetics, Male, Neoplasm Proteins, Neoplasms, Multiple Primary, Oncogene Proteins, Fusion genetics, Orbital Neoplasms congenital, Orbital Neoplasms genetics, Pancreatic Neoplasms congenital, Pancreatic Neoplasms genetics, Transcription Factors genetics, Translocation, Genetic, Carcinoma pathology, Liver Neoplasms pathology, Nuclear Proteins genetics, Oncogene Proteins genetics, Orbital Neoplasms pathology, Pancreatic Neoplasms pathology
- Abstract
NUT midline carcinoma (NMC) is a rare and aggressive malignant epithelial tumor defined by rearrangement of the NUT gene on chromosome 15. In two thirds of cases, NUT is involved in a balanced translocation with BDR4 on chromosome 19, while in the remaining cases, NUT is rearranged with variant fusion partners such as BRD3. These undifferentiated tumors primarily affect midline structures, usually in the upper aerodigestive tract and mediastinum. Most reported cases have followed a rapidly lethal clinical course. We report the clinical and pathological findings of NMC in the youngest patients identified so far. The 1st case involves a newborn who presented with a supraorbital mass and extensive multiorgan involvement, including the spine, lungs, liver, pancreas, adrenal glands, and subcutaneous tissue. The 2nd patient was a 2-year-old male with an abdominal mass involving the liver and pancreas with pulmonary metastasis. Histopathological analysis of both tumors showed undifferentiated malignant neoplasms, and immunohistochemistry showed positivity for epithelial markers. Both tumors demonstrated t(15;19), and immunohistochemistry with NUT monoclonal antibodies and fluorescent in situ hybridization confirmed NUT rearrangement. The patients died from disease at 1 and 2 months postpresentation. Thus far, 25 cases have been reported, including our 2 current cases. Presentation ages range from 0 to 78 years (mean, 23 years). Herein, we report the 2 youngest reported cases of NMC, including the 1st congenital case and the 1st case arising within the liver/pancreas. Increased awareness and further molecular studies are required for a better understanding of NMC pathobiology and improved therapeutic outcomes.
- Published
- 2010
- Full Text
- View/download PDF
13. The role of CD11c expression in the diagnosis of mantle cell lymphoma.
- Author
-
Kraus TS, Sillings CN, Saxe DF, Li S, and Jaye DL
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Separation, Female, Flow Cytometry, Humans, Immunohistochemistry, Immunophenotyping, In Situ Hybridization, Fluorescence, Male, Middle Aged, Biomarkers, Tumor immunology, CD11c Antigen biosynthesis, Lymphoma, Mantle-Cell diagnosis, Lymphoma, Mantle-Cell metabolism
- Abstract
Flow cytometric immunophenotyping (FCI) aids in the differentiation of chronic lymphocytic leukemia (CLL) from mantle cell lymphoma (MCL); however, overlapping phenotypes may occur. CD11c expression has been reported in up to 90% of CLL cases but has rarely been reported in MCL. Whether CD11c can be used to exclude MCL has not been directly addressed. FCI reports were reviewed for 90 MCL cases (44 patients) and 355 CLL/small lymphocytic lymphoma (SLL) cases (158 patients). MCL cases were confirmed by cyclin D1 immunoreactivity and/or t(11;14) detection by karyotyping or fluorescence in situ hybridization. Cases with typical MCL immunophenotypes did not express CD11c. The 2 MCL cases displaying dim CD11c positivity (2 of 44 patients) expressed other markers not typical of MCL. CD11c was detected in 96 (27.0%) of 355 cases of CLL/SLL representing 53 of 158 patients. CD11c expression is rare in MCL and may aid in differentiation of CD5+ B-cell neoplasms, particularly when small samples limit further ancillary testing.
- Published
- 2010
- Full Text
- View/download PDF
14. A novel flow cytometric antibody panel for distinguishing Burkitt lymphoma from CD10+ diffuse large B-cell lymphoma.
- Author
-
Schniederjan SD, Li S, Saxe DF, Lechowicz MJ, Lee KL, Terry PD, and Mann KP
- Subjects
- Adult, Aged, Biomarkers, Tumor metabolism, Burkitt Lymphoma immunology, Burkitt Lymphoma metabolism, Child, Preschool, Diagnosis, Differential, Female, Humans, Immunophenotyping, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse metabolism, Male, Middle Aged, Antibodies, Monoclonal immunology, Antibodies, Neoplasm immunology, Burkitt Lymphoma pathology, Flow Cytometry methods, Lymphoma, Large B-Cell, Diffuse pathology, Neprilysin metabolism
- Abstract
Rapid and accurate differential diagnosis between Burkitt lymphoma (BL) and CD10+ diffuse large B-cell lymphoma (DLBCL) is imperative because their treatment differs. Recent studies have characterized several antigens differentially expressed in these 2 types of lymphoma. Our goal was to determine whether use of these markers would aid in the differential diagnosis of BL vs CD10+ DLBCL by flow cytometric immunophenotyping (FCI). Twenty-three cases of CD10+ B-cell lymphomas with available cryopreserved samples were identified (13 BL and 10 CD10+ DLBCL). Multiparameter FCI was performed using the following antibodies: CD18, CD20, CD43, CD44, and CD54 and isotype controls. Expression of CD44 and CD54 was detected at a significantly lower level in BL compared with CD10+ DLBCL (P = .001 and P = .01, respectively). There was not a significant difference in expression of CD18 and CD43. Our data show that expression of CD44 and CD54 differs significantly between BL and CD10+ DLBCL.
- Published
- 2010
- Full Text
- View/download PDF
15. Detection of mosaicism in amniotic fluid cultures: a CYTO2000 collaborative study.
- Author
-
Ing PS, Van Dyke DL, Caudill SP, Reidy JA, Bice G, Bieber FR, Buchanan PD, Carroll AJ, Cheung SW, DeWald G, Donahue RP, Gardner HA, Higgins J, Hsu LY, Jamehdor M, Keitges EA, Laundon CH, Luthardt FW, Mascarello J, May KM, Meck JM, Morton C, Patil S, Peakman D, Pettenati MJ, Rao N, Sanger WG, Saxe DF, Schwartz S, Sekhon GS, Vance GH, Wyandt HE, Yu CW, Zenger-Hain J, and Chen AT
- Subjects
- Binomial Distribution, Cells, Cultured, Chi-Square Distribution, Cytogenetic Analysis standards, Female, Humans, Karyotyping methods, Pregnancy, Prenatal Diagnosis standards, Amniotic Fluid cytology, Cytogenetic Analysis methods, Guidelines as Topic standards, Mosaicism, Prenatal Diagnosis methods
- Abstract
Purpose: To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic fluid cultures are based., Methods: Data from 653 cases of amniotic fluid mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test was used to compare the observed number of mosaic cases with the expected number based on binomial distribution theory., Results: Comparison of observed data from the in situ colony cases with the expected distribution of cases detected based on the binomial distribution did not reveal a significant difference (P = 0.525)., Conclusions: The empirical data fit the binomial distribution. Therefore, binomial theory can be used as an initial discussion point for determining whether ACMG Standards and Guidelines are adequate for detecting mosaicism.
- Published
- 1999
- Full Text
- View/download PDF
16. Unique mosaicism of tetraploidy and trisomy 8: clinical, cytogenetic, and molecular findings in a live-born infant.
- Author
-
Roberts HE, Saxe DF, Muralidharan K, Coleman KB, Zacharias JF, and Fernhoff PM
- Subjects
- Adult, Face abnormalities, Female, Humans, Infant, Male, Trisomy, Abnormalities, Multiple genetics, Chromosomes, Human, Pair 8, Mosaicism, Polyploidy
- Abstract
We report on a live-born infant with mosaicism of tetraploidy and trisomy 8 who had craniofacial abnormalities, cardiac and genitourinary defects, agenesis of the corpus callosum, and anomalies of limbs. The infant died at age 14 weeks. Molecular studies were done on peripheral blood lymphocytes and cultured amniocytes to determine the origin of the cytogenetic abnormalities. On the basis of the results, we describe a possible mechanism to explain these abnormalities. To our knowledge, this infant represents the first reported case of mosaic trisomy 8 with a tetraploid cell line.
- Published
- 1996
- Full Text
- View/download PDF
17. Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: a collaborative study.
- Author
-
Hsu LY, Yu MT, Richkind KE, Van Dyke DL, Crandall BF, Saxe DF, Khodr GS, Mennuti M, Stetten G, Miller WA, and Priest JH
- Subjects
- Chromosome Inversion, Female, Gene Deletion, Humans, Isochromosomes, Karyotyping, Phenotype, Pregnancy, Pregnancy Outcome, Ring Chromosomes, Sex Chromosome Aberrations diagnosis, Translocation, Genetic, Trisomy, Amniocentesis, Chromosome Aberrations, Mosaicism
- Abstract
Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.
- Published
- 1996
- Full Text
- View/download PDF
18. Confirmation of CVS mosaicism.
- Author
-
May KM, Saxe DF, and Priest JH
- Subjects
- Chorionic Villi Sampling, Female, Humans, Karyotyping, Placenta cytology, Pregnancy, Pregnancy Trimester, First, Fetal Growth Retardation diagnosis
- Published
- 1992
- Full Text
- View/download PDF
19. Localization of the human myelin basic protein gene (MBP) to region 18q22----qter by in situ hybridization.
- Author
-
Saxe DF, Takahashi N, Hood L, and Simon MI
- Subjects
- Animals, Autoradiography, Cloning, Molecular, DNA genetics, Genes, Humans, Karyotyping, Mice, Nucleic Acid Hybridization, Rats, Chromosome Mapping, Chromosomes, Human, 16-18, Myelin Basic Protein genetics
- Abstract
A restriction endonuclease fragment derived from a cloned portion of human genomic DNA corresponding to the myelin basic protein gene has been used to map the position of this gene by in situ hybridization to human metaphase chromosomes. Ten percent of the radioactively labeled sites observed were on chromosome 18. Eighty-four percent of the grains on chromosome 18 were located within the region corresponding to 18q22----qter. This represents a greater than 10-fold increase in labeling at this position over the background grain distribution found along all of the other chromosomes.
- Published
- 1985
- Full Text
- View/download PDF
20. Trisomy of chromosome 6.15 is not necessary for proliferation of AKR(Rb6.15)1Ald lymphoma cells.
- Author
-
Boggs SS, Patrene KD, Downer WR, Schwartz GN, and Saxe DF
- Subjects
- Animals, Female, Karyotyping, Male, Mice, Mice, Inbred AKR, Neoplasm Transplantation, Neoplasms, Experimental genetics, Lymphoma genetics, Trisomy
- Abstract
By utilizing a unique AKR(Rb6.15)Ald (AKRb) mouse line we have been able to determine the incidence and frequency of cells with and without abnormalities of chromosome number (specifically trisomy 6.15) in spontaneous and transplanted lymphoma. The transplanted lymphoma cells were easily distinguished from the normal cells of AKR/J recipients by the presence in diploid cells of 2 metacentric and 36 acrocentric chromosomes. The majority of the cells from 17 normal control AKRb mice were diploid and trisomy 6.15 (3 metacentric and 36 acrocentric chromosomes) was not seen. In 73% of the 59 AKRb mice with spontaneous lymphoma, the majority of cells were diploid. In 54% of the mice none of the cells had trisomy 6.15, and in 22% of these mice a majority (greater than 50%) of cells had trisomy 6.15. In order to determine which of the cells from AKRb mice with spontaneous lymphoma were malignant, they were transplanted into normal young AKR/J recipient mice, and when lymphoma developed in recipients, their cells were analyzed. The majority of first passage lymphoma cells from 30 recipient mice were donor-type and the majority of these donor cells were diploid. Ten (17%) of these recipients had a majority of cells with trisomy 6.15. In order to further determine whether or not trisomic lymphoma cells had a different proliferative rate than diploid lymphoma cells, eight first passage recipient mice were used to start sequential passage lines. In two diploid lines and four trisomic lines, the same relative frequency of the trisomy was maintained in the sequential passages. However, in two trisomic lines, the frequency of lymphoma cells with three metacentric chromosomes diminished after passage. These studies suggest that aneuploidy is not necessary for proliferation of lymphoma and that diploid cells are a major part of the malignant cell population.
- Published
- 1983
- Full Text
- View/download PDF
21. In vitro clonal assay for human metastatic melanoma cells.
- Author
-
Meyskens FL Jr, Soehnlen BJ, Saxe DF, Casey WJ, and Salmon SE
- Subjects
- Cells, Cultured, Chromosome Aberrations, Clone Cells, Humans, Lymph Nodes pathology, Macrophages physiology, Melanoma ultrastructure, Neoplasm Metastasis pathology, Skin pathology, Melanoma pathology
- Abstract
An in vitro assay for clonogenic tumor cells was applied to human metastatic melanomas. Melanoma colony formation was observed in 22 of 33 samples obtained from a variety of involved tissues. The melanocytic tumor origin of colonies was established by serial observations by inverted light microscopy, staining of fixed colonies for melanin, and cytological and karyotypic analysis of cells within colonies. Two morphologically distinct types of colonies were identified, one consisting of light large cells and the second of dark small cells. Investigations of factors which modulate growth and differentiation of clonogenic melanoma cells may provide a clearer understanding of this neoplasm.
- Published
- 1981
22. Transplantation of chromosomally marked syngeneic marrow cells into mice not subjected to hematopoietic stem cell depletion.
- Author
-
Saxe DF, Boggs SS, and Boggs DR
- Subjects
- Animals, Bone Marrow Cells, Chimera, Female, Hematopoietic Stem Cells cytology, Male, Mice, Mice, Inbred AKR, Mice, Inbred C57BL, Mice, Inbred CBA, Sex Factors, Spleen cytology, Bone Marrow Transplantation, Transplantation, Isogeneic
- Abstract
The percentage of donor-host chimerism was determined 4-6 weeks or six months after injection of normal bone marrow cells into normal syngeneic or coisogeneic recipient mice. Donor-recipient pairs had chromosome markers that provided easy identification of metaphase cells. The percentage of donor cells in marrow or spleen ranged from 0 to 16% and this percentage was independent of the age of recipient or attempts to stimulate hematopoiesis in donor and/or host mice. In adult C57BL/6 mice there was a roughly linear dose-response relationship between cell dose and percentage of chimerism. There was no apparent dose-response relationship for AKR mice. The percentage of donor cells in the spleen was correlated to that seen in the marrow of recipients. Neonatal mice given the same intraperitoneal marrow cell dose as weanlings, but a larger number of cells relative to their own marrow mass, did not show a larger percentage of chimerism than weanlings. Similarly, weanlings given the same intravenous dose as adults showed no greater degree of chimerism than adults. Temporary anemia, induced by bleeding donors prior to cell collection, or more chronic hemopoietic stimulus (produced by injecting recipients with phenylhydrazine prior to cell injection with subsequent bleeding at intervals) did not result in an increased percentage of chimerism. These results indicate that there are "empty" sites in bone marrow of normal mice in which injected hematopoietic stem cells can lodge and grow.
- Published
- 1984
23. Aging and hematopoiesis. II. The ability of bone marrow cells from young and aged mice to cure and maintain cure in W/Wv.
- Author
-
Boggs DR, Saxe DF, and Boggs SS
- Subjects
- Anemia, Macrocytic blood, Anemia, Macrocytic physiopathology, Animals, Bone Marrow physiology, Bone Marrow Cells, Cell Survival, Colony-Forming Units Assay, Female, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells physiology, Male, Mice, Mice, Mutant Strains, Spleen cytology, Aging, Anemia, Macrocytic therapy, Bone Marrow Transplantation, Hematopoiesis, Hematopoietic Stem Cell Transplantation
- Abstract
The proliferative ability of hematopoietic stem cells (HSC) was compared in young and aged mice. Infusion of coisogeneic marrow cures the hematopoietic defect of the W/Wv, a mouse with a recessively inherited defect in stem cells, including HSC. W/Wv were cured with equal frequency by relatively small doses of marrow (5 X 10(4) nucleated cells, an average of 2-3 "curative" HSC per aliquot) from 3-month-old or 27-month-old +/+ donors. After functioning in the originally cured W/Wv for 26 months, the marrow was used to cure other W/Wv. After functioning in secondary recipients for 16 months, it was, in turn, used to cure still other W/Wv. There was no difference between "old" and "young" bone marrow with respect to the frequency of cure in W/Wv, the duration of cure--or, in regard to marrow from cured W/Wv, the number of nucleated and peroxidase-positive cells per humerus and the number of cells capable of producing spleen colonies in irradiated recipients. Thus, these studies fail to disclose any evidence for a proliferative limitation for old as compared to young HSC.
- Published
- 1984
24. Hematopoietic stem cells with high proliferative potential. Assay of their concentration in marrow by the frequency and duration of cure of W/Wv mice.
- Author
-
Boggs DR, Boggs SS, Saxe DF, Gress LA, and Canfield DR
- Subjects
- Animals, Cell Division, Hematopoietic Stem Cell Transplantation, Mice, Mice, Inbred Strains, Anemia, Macrocytic therapy, Hematopoietic Stem Cells cytology
- Abstract
THIS STUDY WAS DESIGNED TO APPROACH TWO PRIMARY QUESTIONS CONCERNING HEMATOPOIETIC STEM CELLS (HSC) IN MICE: what is the concentration of HSC with extensive proliferative potential in marrow, and how long can an HSC continue to function in an intact animal? The assay system was the W/W(v) mouse, a mouse with an inherited HSC defect, reflected in a reduction in all myeloid tissue and most particularly in a macrocytic anemia.A single chromosomally marked HSC will reconstitute the defective hematopoietic system of the W/W(v). The concentration of HSC in normal littermate (+/+) marrow was assayed by limiting dilution calculation using cure of W/W(v) as an end point (correction of anemia and erythrocytes' macrocytosis) and found to be approximately 10/10(5). This is significantly less than spleen colony forming cell (CFU-S) concentration: approximately 220/10(5) in +/+ and ranging from 50 to 270/10(5) in various other studies. Blood values were studied at selected intervals for as long as 26 mo. Of 24 initially cured mice, which were observed for at least 2 yr, 75% remained cured. However, of all cured mice, 17 lost the cure, returning to a macrocytic anemic state. Cured mice had normal numbers of nucleated and granulocytic cells per humerus and a normal concentration of CFU-S. However, cure of secondary W/W(v) recipients by this marrow was inefficient compared with the original +/+ marrow. These studies suggest the CFU-S assay over-estimates extensively proliferating HSC or perhaps does not assay such a cell. A single such HSC can not only cure a W/W(v), but can sustain the cure for 2 yr or more, despite a relative deficit of cells capable of curing other W/W(v). However, the duration of sustained cure may be finite.
- Published
- 1982
- Full Text
- View/download PDF
25. Effect of rabbit antimouse brain serum on marrow cells capable of curing W/Wv mice.
- Author
-
Saxe DF, Boggs DR, Monette FC, and Boggs SS
- Subjects
- Animals, Colony-Forming Units Assay, Female, Male, Mice, Rabbits immunology, Time Factors, Transplantation, Isogeneic, Bone Marrow Cells, Brain immunology, Hematopoietic Stem Cells physiology, Immune Sera, Mice, Inbred Strains immunology
- Abstract
The W/Wv mouse has a recessively inherited defect in hematopoietic stem cells (HSC) but can be cured of its hematopoietic abnormalities by infusion of marrow from a co-isogeneic, +/+ mouse. The "curative" cell for the W/Wv is thought to be a subcompartment of the HSC that is capable of forming hematopoietic spleen colonies (CFU-S) in irradiated mice. The curative HSC must have a very high proliferative potential and it is known that HSC with variable degrees of proliferative potential are found within the CFU-S compartment. Rabbit antimouse brain serum (RAMBS) was used to treat +/+ marrow and its effect upon CFU-S and upon curative cells was compared with the effect of normal rabbit serum (NRS) or of sham treatment. CFU-S were reduced to 70%-79% of control by NRS and to 8%-9% by RAMBS. Curative cells for the W/Wv were not detectably reduced by NRS; they were reduced by RAMBS, but to only approximately 20%-30% of control. Thus, it appeared to a certain degree that RAMBS spared HSC with a high proliferative potential when compared with its effect on the entire CFU-S compartment.
- Published
- 1985
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.