335 research outputs found
Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis
Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma
Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis
Early diagnosis improves melanoma survival, yet the histopathological diagnosis of cutaneous primary melanoma can be challenging, even for expert dermatopathologists. Analysis of epigenetic alterations, such as DNA methylation, that occur in melanoma can aid in its early diagnosis. Using a genome-wide methylation screening, we assessed CpG methylation in a diverse set of 89 primary invasive melanomas, 73 nevi, and 41 melanocytic proliferations of uncertain malignant potential, classified based on interobserver review by dermatopathologists. Melanomas and nevi were split into training and validation sets. Predictive modeling in the training set using ElasticNet identified a 40-CpG classifier distinguishing 60 melanomas from 48 nevi. High diagnostic accuracy (area under the receiver operator characteristic curve = 0.996, sensitivity = 96.6%, and specificity = 100.0%)was independently confirmed in the validation set (29 melanomas, 25 nevi)and other published sample sets. The 40-CpG melanoma classifier included homeobox transcription factors and genes with roles in stem cell pluripotency or the nervous system. Application of the 40-CpG melanoma classifier to the diagnostically uncertain samples assigned melanoma or nevus status, potentially offering a diagnostic tool to assist dermatopathologists. In summary, the robust, accurate 40-CpG melanoma classifier offers a promising assay for improving primary melanoma diagnosis
Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas
Cutaneous melanoma can be lethal even if detected at an early stage. Epigenetic profiling may facilitate the identification of aggressive primary melanomas with unfavorable outcomes. We performed clustering of whole-genome methylation data to identify subclasses that were then assessed for survival, clinical features, methylation patterns, and biological pathways. Among 89 cutaneous primary invasive melanomas, we identified three methylation subclasses exhibiting low methylation, intermediate methylation, or hypermethylation of CpG islands, known as the CpG island methylator phenotype (CIMP). CIMP melanomas occurred as early as tumor stage 1b and, compared with low-methylation melanomas, were associated with age at diagnosis ≥65 years, lentigo maligna melanoma histologic subtype, presence of ulceration, higher American Joint Committee on Cancer stage and tumor stage, and lower tumor-infiltrating lymphocyte grade (all P < 0.05). Patients with CIMP melanomas had worse melanoma-specific survival (hazard ratio = 11.84; confidence interval = 4.65‒30.20) than those with low-methylation melanomas, adjusted for age, sex, American Joint Committee on Cancer stage, and tumor-infiltrating lymphocyte grade. Genes hypermethylated in CIMP compared with those in low-methylation melanomas included PTEN, VDR, PD-L1, TET2, and gene sets related to development/differentiation, the extracellular matrix, and immunity. CIMP melanomas exhibited hypermethylation of genes important in melanoma progression and tumor immunity, and although present in some early melanomas, CIMP was associated with worse survival independent of known prognostic factors
Global Search for New Physics with 2.0/fb at CDF
Data collected in Run II of the Fermilab Tevatron are searched for
indications of new electroweak-scale physics. Rather than focusing on
particular new physics scenarios, CDF data are analyzed for discrepancies with
the standard model prediction. A model-independent approach (Vista) considers
gross features of the data, and is sensitive to new large cross-section
physics. Further sensitivity to new physics is provided by two additional
algorithms: a Bump Hunter searches invariant mass distributions for "bumps"
that could indicate resonant production of new particles; and the Sleuth
procedure scans for data excesses at large summed transverse momentum. This
combined global search for new physics in 2.0/fb of ppbar collisions at
sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D
Rapid Communication
Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for the production of neutral Higgs bosons decaying into
tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The
data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by
the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the
95% C.L. on the product of production cross section and branching ratio for a
scalar resonance decaying into tautau pairs, and we then interpret these limits
as limits on the production of Higgs bosons in the minimal supersymmetric
standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL
Measurement of the photon-jet production differential cross section in collisions at \sqrt{s}=1.96~\TeV
We present measurements of the differential cross section dsigma/dpT_gamma
for the inclusive production of a photon in association with a b-quark jet for
photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for
photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is
the photon transverse momentum. The b-quark jets are required to have pT>15 GeV
and rapidity |y_jet| < 1.5. The results are based on data corresponding to an
integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the
Fermilab Tevatron Collider at sqrt(s)=1.96 TeV. The measured cross
sections are compared with next-to-leading order perturbative QCD calculations
using different sets of parton distribution functions as well as to predictions
based on the kT-factorization QCD approach, and those from the Sherpa and
Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.
Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV
We present final searches of the anomalous gammaWW and ZWW trilinear gauge
boson couplings from WW and WZ production using lepton plus dijet final states
and a combination with results from Wgamma, WW, and WZ production with leptonic
final states. The analyzed data correspond to up to 8.6/fb of integrated
luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96
TeV. We set the most stringent limits at a hadron collider to date assuming two
different relations between the anomalous coupling parameters
Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2
TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154,
-0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization,
and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings
parameterization. We also present the most stringent limits of the W boson
magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL
Search for pair production of the scalar top quark in muon+tau final states
We present a search for the pair production of scalar top quarks
(), the lightest supersymmetric partners of the top quarks, in
collisions at a center-of-mass energy of 1.96 TeV, using data
corresponding to an integrated luminosity of {7.3 } collected with the
\dzero experiment at the Fermilab Tevatron Collider. Each scalar top quark is
assumed to decay into a quark, a charged lepton, and a scalar neutrino
(). We investigate final states arising from and
. With no significant excess of events observed above the
background expected from the standard model, we set exclusion limits on this
production process in the (,) plane.Comment: Submitted to Phys. Lett.
Measurements of inclusive W+jets production rates as a function of jet transverse momentum in ppbar collisions at sqrt{s}=1.96 TeV
This Letter describes measurements of inclusive W (--> e nu) + n jet cross
sections (n = 1-4), presented as total inclusive cross sections and
differentially in the nth jet transverse momentum. The measurements are made
using data corresponding to an integrated luminosity of 4.2 fb-1 collected by
the D0 detector at the Fermilab Tevatron Collider, and achieve considerably
smaller uncertainties on W +jets production cross sections than previous
measurements. The measurements are compared to next-to-leading order
perturbative QCD (pQCD) calculations in the n =1-3 jet multiplicity bins and to
leading order pQCD calculations in the 4-jet bin. The measurements are
generally in agreement with pQCD predictions, although certain regions of phase
space are identified where the calculations could be improved
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