29 research outputs found

    Simplified microsatellite instability detection protocol provides equivalent sensitivity to robust detection strategies in Lynch syndrome patients

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    Objective: Germline mutations in mismatch repair (MMR) genes cause Lynch syndrome (LS). LS is an inherited disease, and an important consequence of MMR deficiency is microsatellite instability (MSI) phenotype. MSI phenotype influences the efficacy of 5 fluorouracil (5-FU) chemotherapy. Reproducible, cost effective, and easy to perform laboratory tests are required to include MSI detection in routine laboratory practice. Evaluation of CAT25 as monomorphic short tandem repeat sequence enables CAT25 to be an efficient screening tool among hereditary nonpolyposis colorectal cancer (HNPCC) patients compared with other methods used currently. Methods: Based on Amsterdam II criteria, 31 patients in 31 families were shortlisted from a total number of 1,659 colorectal cancer patients. MSI status was examined in these patients using CAT25 and a commercially available Promega MSI five-marker-based detection system as well as immunohistochemical (IHC) staining of four important MMR proteins. Patients were scored as high microsatellite instable (MSI-H), low (MSI-L), or stable (MSS). MSI status determined by CAT25 single mononucleotide marker was compared with that of five mononucleotide markers, Promega commercial kit, and IHC method. Results: MMR protein deficiency was observed on 7/31 probands using IHC methodology and 6/31 categorized as MSI-H using commercial kit or CAT25 single marker. The sensitivity and specificity of the CAT25 single marker were the same as those detected by five-marker Promega commercial kit in our patients. Conclusions: Based on our results, the performance of the CAT25 single mononucleotide marker for MSI status determination in our HNPCC patients is the same as that of the five-marker-based commercial kit

    MT1XT20 single quasi-monomorphic mononucleotide marker for detection of microsatellite instability in iranian patients with hereditary nonpolyposis colorectal cancer (HNPCC)

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    Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary or sporadic, demonstrate better prognosis, altered response to fluorouracil (5FU) chemotherapy and altered operative approach. It is now recommended to perform MSI testing for all new cases of colorectal cancers regardless of being categorized as hereditary or sporadic. This study aimed to evaluate MT1XT20 mononucleotide marker in Iranian patients with hereditary nonpolyposis colorectal cancer (HNPCC). The samples were further characterized using Promega five-marker MSI testing panel and immunohistochemical (IHC) technique. Methods: MT1XT20 mononucleotide marker and commercially available kit (Promega, USA) incorporating five quasi-monomorphic markers were studied in 20 cases of HNPCC using polymerase chain reaction (PCR) technique. IHC was performed to evaluate the status of all four important mismatch repair (MMR) proteins, too. Findings: Eight (40%), seven (35%) and five (25%) cases showed MSI using Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker with instability in all 8 samples (100%) was the most instable marker. NR24 and NR21 markers showed instability in 7 cases (87.5%); BAT25 and MONO 27 markers were instable in 6 (75.0%) and 5 (62.5%) specimens, respectively. Conclusion: Although MT1XT20 is considered as a valid single marker in Italian population, it seems this is not hold true about the Iranian patients. Instead, BAT26 among the markers included in Promega MSI testing was shown instability in all 8 samples of MSI-H colorectal cancer (CRC). Therefore, it may be concluded that BAT26 alone is as efficient as the cohort of five markers in Iranian patients. © 2016, Isfahan University of Medical Sciences(IUMS). All rights reserved

    Evaluation of MT1XT20 single quasi-monomorphic mononucleotide marker for characterizing microsatellite instability in persian lynch syndrome patients

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    Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20. Materials and Methods: Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data. Results: Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%). Conclusions: Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients

    The Ionizing Photon Production Efficiency (ξion\xi_{ion}) Of Lensed Dwarf Galaxies At z2z \sim 2

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    We measure the ionizing photon production efficiency (ξion\xi_{ion}) of low-mass galaxies (107.810^{7.8}-109.810^{9.8} MM_{\odot}) at 1.4<z<2.71.4<z<2.7, allowing us to better understand the contribution of dwarf galaxies to the ionizing background and cosmic reionization. We target galaxies that are magnified by the strong lensing galaxy clusters Abell 1689, MACS J0717, and MACS J1149. We utilize Keck/MOSFIRE spectra to measure optical nebular emission line fluxes and HST imaging to measure the rest-UV and rest-optical photometry. We present two methods of stacking. First, we take the average of the log(LHα_{H\alpha} /LUV_{UV}) of galaxies in our sample to determine the typical log(ξion\xi_{ion}). Second, we take the logarithm of the total LHα_{H\alpha} over the total LUV_{UV}. We prefer the latter as it provides the total ionizing UV luminosity density of galaxies when multiplied by the non-ionizing UV luminosity density from the UV luminosity function. log(ξion\xi_{ion}) calculated from the second method is \sim 0.2 dex higher than the first method. We do not find any strong dependence between log(ξion\xi_{ion}) and stellar mass, MUV_{UV} or UV spectral slope (β\beta). We report a value of log(ξion\xi_{ion}) 25.47±0.09\sim25.47\pm 0.09 for our UV-complete sample (22<MUV<17.3-22<M_{UV}<-17.3) and 25.37±0.11\sim25.37\pm0.11 for our mass-complete sample (7.8<log(M)<9.8)7.8<\log(M_*)<9.8). These values are consistent with measurements of more massive, more luminous galaxies in other high-redshift studies that use the same stacking technique. Our log(ξion\xi_{ion}) is 0.20.30.2-0.3 dex higher than low-redshift galaxies of similar mass, indicating an evolution in the stellar properties, possibly due to metallicity, age, or the prevalence of binary stars. We also find a correlation between log(ξion\xi_{ion}) and the equivalent widths of Hα\alpha and [OIII]λ\lambda5007 fluxes, confirming that these equivalent widths can be used to estimate ξion\xi_{ion}.Comment: 16 pages, 6 figures, 1 table, Accepted in Ap

    The Recent Burstiness of Star Formation in Galaxies at z ~ 4.5 from Hα Measurements

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    The redshift range z = 4–6 marks a transition phase between primordial and mature galaxy formation in which galaxies considerably increase their stellar mass, metallicity, and dust content. The study of galaxies in this redshift range is therefore important to understanding early galaxy formation and the fate of galaxies at later times. Here, we investigate the burstiness of the recent star formation history (SFH) of 221z ~ 4.5 main-sequence galaxies at log(M/M⊙) > 9.7 by comparing their ultra-violet (UV) continuum, Hα luminosity, and Hα equivalent-width (EW). The Hα properties are derived from the Spitzer [3.6 μm]−[4.5 μm] broadband color, thereby properly taking into account model and photometric uncertainties. We find a significant scatter between Hα- and UV-derived luminosities and star formation rates (SFRs). About half of the galaxies show a significant excess in Hα compared to expectations from a constant smooth SFH. We also find a tentative anticorrelation between Hα EW and stellar mass, ranging from 1000 Å at log(M/M⊙) 11. Consulting models suggests that most z ~ 4.5 galaxies had a burst of star formation within the last 50 Myr, increasing their SFRs by a factor of >5. The most massive galaxies on the other hand might decrease their SFRs and may be transitioning to a quiescent stage by z = 4. We identify differential dust attenuation (f) between stars and nebular regions as the main contributor to the uncertainty. With local galaxies selected by increasing Hα EW (reaching values similar to high-z galaxies), we predict that f approaches unity at z > 4, consistent with the extrapolation of measurements out to z = 2

    Shock cooling of a red-supergiant supernova at redshift 3 in lensed images

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    The core-collapse supernova of a massive star rapidly brightens when a shock, produced following the collapse of its core, reaches the stellar surface. As the shock-heated star subsequently expands and cools, its early-time light curve should have a simple dependence on the progenitor's size and therefore final evolutionary state. Measurements of the progenitor's radius from early light curves exist for only a small sample of nearby supernovae, and almost all lack constraining ultraviolet observations within a day of explosion. The several-day time delays and magnifying ability of galaxy-scale gravitational lenses, however, should provide a powerful tool for measuring the early light curves of distant supernovae, and thereby studying massive stellar populations at high redshift. Here we analyse individual rest-frame ultraviolet-through-optical exposures taken with the Hubble Space Telescope that simultaneously capture, in three separate gravitationally lensed images, the early phases of a supernova at redshift z3z \approx 3 beginning within 5.8±3.15.8\pm 3.1 hr of explosion. The supernova, seen at a lookback time of 11.5\sim11.5 billion years, is strongly lensed by an early-type galaxy in the Abell 370 cluster. We constrain the pre-explosion radius to be 533119+154533^{+154}_{-119} solar radii, consistent with a red supergiant. Highly confined and massive circumstellar material at the same radius can also reproduce the light curve, but is unlikely since no similar low-redshift examples are known.Comment: 69 pages, 12 figures/tables (4 main text, 8 extended data). Published in Natur

    Exploring the Correlation between Hα\rm{H}\alpha-to-UV Ratio and Burstiness for Typical Star-forming Galaxies at z2z\sim2

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    The Hα\rm{H}\alpha-to-UV luminosity ratio (L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV)) is often used to probe SFHs of star-forming galaxies and it is important to validate it against other proxies for burstiness. To address this issue, we present a statistical analysis of the resolved distribution of ΣSFR\Sigma_{\rm{SFR}} as well as stellar age and their correlations with the globally measured L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV) for a sample of 310 star-forming galaxies in two redshift bins of 1.37<z<1.701.37 < z < 1.70 and 2.09<z<2.61 2.09 < z < 2.61 observed by the MOSDEF survey. We use the multi-waveband CANDELS/3D-HST imaging of MOSDEF galaxies to construct ΣSFR\Sigma_{\rm{SFR}} and stellar age maps. We analyze the composite rest-frame far-UV spectra of a subsample of MOSDEF targets obtained by the Keck/LRIS, which includes 124 star-forming galaxies (MOSDEF-LRIS) at redshifts 1.4<z<2.61.4 < z < 2.6, to examine the average stellar population properties, and the strength of age-sensitive FUV spectral features in bins of L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV). Our results show no significant evidence that individual galaxies with higher L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV) are undergoing a burst of star formation based on the resolved distribution of ΣSFR\Sigma_{\rm{SFR}} of individual star-forming galaxies. We segregate the sample into subsets with low and high L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV). The high-L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV) subset exhibits, on average, an age of log[Age/yr]\log[\rm{Age/yr}] = 8.0, compared to log[Age/yr]\log[\rm{Age/yr}] = 8.4 for the low-L(Hα)/L(UV)L(\rm H\alpha)/L(\rm UV) galaxies, though the difference in age is significant at only the 2σ2\sigma level. Furthermore, we find no variation in the strengths of Siivλλ1393,1402\lambda\lambda1393, 1402 and Civλλ1548,1550\lambda\lambda1548, 1550 P-Cygni features from massive stars between the two subsamples.Comment: 16 pages, 10 figures, published by the Monthly Notices of the Royal Astronomical Societ

    The Detection of [O III] λ4363 in a Lensed, Dwarf Galaxy at z = 2.59: Testing Metallicity Indicators and Scaling Relations at High Redshift and Low Mass

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    We present Keck/MOSFIRE (Multi-Object Spectrometer for InfraRed Exploration) and Keck/LRIS (Low Resolution Imaging Spectrometer) spectroscopy of A1689-217, a lensed (magnification ~7.9), star-forming (SFR ~ 16 M_☉ yr⁻¹), dwarf (log(M_★/M_☉) = 8.07–8.59) Lyα emitter (EW₀ ~ 138 Å) at z = 2.5918. Dwarf galaxies similar to A1689-217 are common at high redshift and likely responsible for reionization, yet few have been studied with detailed spectroscopy. We report a 4.2σ detection of the electron-temperature-sensitive [O iii] λ4363 emission line and use this line to directly measure an oxygen abundance of 12 + log(O/H) = 8.06 ± 0.12 (~1/4 Z_☉). A1689-217 is the lowest-mass galaxy at z > 2 with an [O iii] λ4363 detection. Using the rest-optical emission lines, we measure A1689-217's other nebular conditions, including electron temperature (T e ([O iii]) ~ 14,000 K), electron density (n e ~ 220 cm⁻³), and reddening (E(B-V) ~ 0.39). We study relations between strong-line ratios and direct metallicities with A1689-217 and other galaxies with [O iii] λ4363 detections at z ~ 0–3.1, showing that the locally calibrated, oxygen-based, strong-line relations are consistent from z ~ 0 to 3.1. We also show additional evidence that the O₃₂ versus R₂₃ excitation diagram can be utilized as a redshift-invariant, direct-metallicity-based, oxygen abundance diagnostic out to z ~ 3.1. From this excitation diagram and the strong-line ratio–metallicity plots, we observe that the ionization parameter at fixed O/H is consistent with no redshift evolution. Although A1689-217 is metal-rich for its M_★ and star formation rate, we find it to be consistent within the large scatter of the low-mass end of the fundamental metallicity relation
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