Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent ...independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other.
ABSTRACT
In this work, we study the formation and chemical evolution of the Galactic bulge with particular focus on the abundance pattern (Mg/Fe versus Fe/H), metallicity, and age distribution ...functions. We consider detailed chemical evolution models for the Galactic bulge and inner disc, with the aim of shedding light on the connection between these components and the origin of bulge stars. In particular, we first present a model assuming a fast and intense star formation, with the majority of bulge stars forming on a time-scale less than 1 Gyr. Then we analyse the possibility of two distinct stellar populations in the bulge, as suggested by Gaia-ESO and APOGEE data. These two populations, one metal poor and the other metal rich, can have had two different origins: (i) the metal rich formed after a stop of ∼250 Myr in the star formation rate of the bulge or (ii) the metal-rich population is made of stars formed in the inner disc and brought into the bulge by the early secular evolution of the bar. We also examine the case of multiple starbursts in the bulge with consequent formation of multiple populations, as suggested by studies of microlensed stars. After comparing model results and observations, we suggest that the most likely scenario is that there are two main stellar populations, both made mainly by old stars (>10 Gyr), with the metal-rich and younger one formed from inner thin disc stars, in agreement with kinematical arguments. However, on the basis of dynamical simulations, we cannot completely exclude that the second population formed after a stop in the star formation during the bulge evolution, so that all the stars formed in situ.
Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and ...TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postulated as the cellular origin of primary SCLC. However, both in lung and many other organs, combined small cell/non‐small cell tumors and secondary transitions from non‐small cell carcinomas upon cancer therapy to neuroendocrine and small cell tumors occur. We define features of “small cell‐ness” based on neuroendocrine markers, characteristic RB1 and TP53 mutations and small cell morphology. Furthermore, here we identify a pathway driving the pathogenesis of secondary SCLC involving inactivating NOTCH mutations, activation of the NOTCH target ASCL1 and canonical WNT‐signaling in the context of mutual bi‐allelic RB1 and TP53 lesions. Additionaly, we explored ASCL1 dependent RB inactivation by phosphorylation, which is reversible by CDK5 inhibition. We experimentally verify the NOTCH‐ASCL1‐RB‐p53 signaling axis in vitro and validate its activation by genetic alterations in vivo. We analyzed clinical tumor samples including SCLC, SCC and pulmonary large cell neuroendocrine carcinomas and adenocarcinomas using amplicon‐based Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. In conclusion, we identified a novel pathway underlying rare secondary SCLC which may drive small cell carcinomas in organs other than lung, as well.
What's new?
Using next generation sequencing and establishing features of ‘small cell‐ness’, we identified a NOTCH‐ASCL1‐RB1‐TP53 signaling axis driving small cell cancers. In contrast to the previously described bi‐allelic RB1/TP53 loss in neuroendocrine stem cells as origin of primary small cell neuroendocrine cancers, the NOTCH‐ASCL1 mediated signaling defines an alternative pathway driving secondary small cell neuroendocrine cancers arising from non‐small cell cancers. Moreover, we show a preclinical rational for therapeutically testing WNT‐inhibitors in small cell cancers.
Gaia Data Release 3 de Laverny, P.; Spagna, A.; Vallenari, A. ...
Astronomy and astrophysics (Berlin),
06/2023, Letnik:
674
Journal Article, Web Resource
Recenzirano
Odprti dostop
Context.
The motion of stars has been used to reveal details of the complex history of the Milky Way, in constant interaction with its environment. Nevertheless, to reconstruct the Galactic history ...puzzle in its entirety, the chemo-physical characterisation of stars is essential. Previous
Gaia
data releases were supported by a smaller, heterogeneous, and spatially biased mixture of chemical data from ground-based observations.
Aims.
Gaia
Data Release 3 opens a new era of all-sky spectral analysis of stellar populations thanks to the nearly 5.6 million stars observed by the Radial Velocity Spectrometer (RVS) and parametrised by the GSP-Spec module. In this work, we aim to demonstrate the scientific quality of
Gaia
’s Milky Way chemical cartography through a chemo-dynamical analysis of disc and halo populations.
Methods.
Stellar atmospheric parameters and chemical abundances provided by
Gaia
DR3 spectroscopy are combined with DR3 radial velocities and EDR3 astrometry to analyse the relationships between chemistry and Milky Way structure, stellar kinematics, and orbital parameters.
Results.
The all-sky
Gaia
chemical cartography allows a powerful and precise chemo-dynamical view of the Milky Way with unprecedented spatial coverage and statistical robustness. First, it reveals the strong vertical symmetry of the Galaxy and the flared structure of the disc. Second, the observed kinematic disturbances of the disc – seen as phase space correlations – and kinematic or orbital substructures are associated with chemical patterns that favour stars with enhanced metallicities and lower
α
/Fe abundance ratios compared to the median values in the radial distributions. This is detected both for young objects that trace the spiral arms and older populations. Several
α
, iron-peak elements and at least one heavy element trace the thin and thick disc properties in the solar cylinder. Third, young disc stars show a recent chemical impoverishment in several elements. Fourth, the largest chemo-dynamical sample of open clusters analysed so far shows a steepening of the radial metallicity gradient with age, which is also observed in the young field population. Finally, the
Gaia
chemical data have the required coverage and precision to unveil galaxy accretion debris and heated disc stars on halo orbits through their
α
/Fe ratio, and to allow the study of the chemo-dynamical properties of globular clusters.
Conclusions.
Gaia
DR3 chemo-dynamical diagnostics open new horizons before the era of ground-based wide-field spectroscopic surveys. They unveil a complex Milky Way that is the outcome of an eventful evolution, shaping it to the present day.
Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different ...morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur, to include Sertoli cell tumors and gynandroblastomas. Our results suggest that DICER1 mutations may not have a role in testicular sex cord-stromal tumorigenesis.
Abstract
We report metallicities for three ∼Gyr-old stars in the Milky Way nuclear star cluster (NSC) using high-resolution near-infrared spectroscopy. We derive effective temperatures from a ...calibration with Sc line strength, which yields results in good agreement with other methods, and metallicities from spectral fits to Fe
i
lines. Our derived metallicities range from −1.2 < Fe/H < + 0.5, a span of 1.7 dex. In addition we use isochrone projection to obtain masses of 1.6–4.3
M
⊙
, and ages assuming single-star evolution. The oldest of these stars is 1.5 Gyr while the youngest and most metal-rich is only 100 Myr. The wide range in metallicity poses interesting questions concerning the chemical evolution and enrichment of the NSC and adds to the evidence for the presence of a young, metal-rich population in the NSC. We suggest that the candidate intermediate-age, metal-poor (Fe/H = −1.2) star may be best explained as a blue straggler from an underlying old population.
Context. With the existing and upcoming large multifibre low-resolution spectrographs, the question arises of how precise stellar parameters such as Teff and Fe/H can be obtained from low-resolution ...K-band spectra with respect to traditional photometric temperature measurements. Until now, most of the effective temperatures in Galactic bulge studies come directly from photometric techniques. Uncertainties in interstellar reddening and in the assumed extinction law could lead to large systematic errors (>200 K). Aims. We obtain and calibrate the relation between Teff and the 12CO first overtone bands for M giants in the Galactic bulge covering a wide range in metallicity. Methods. We used low-resolution spectra for 20 M giants with well-studied parameters from photometric measurements covering the temperature range 3200 <Teff< 4500 K and a metallicity range from 0.5 dex down to −1.2 dex and study the behaviour of Teff and Fe/H on the spectral indices. Results. We find a tight relation between Teff and the 12CO(2−0) band with a dispersion of 95 K and between Teff and the 12CO(3−1) with a dispersion of 120 K. We do not find any dependence of these relations on the metallicity of the star, which makes them attractive for Galactic bulge studies. This relation is also not sensitive to the spectral resolution, which allows this relation to be applied in a more general way. We also find a correlation between the combination of the Na i, Ca i, and the 12CO band with the metallicity of the star. However, this relation is only valid for subsolar metallicities. Conclusions. We show that low-resolution spectra provide a powerful tool for obtaining effective temperatures of M giants. We show that this relation does not depend on the metallicity of the star within the investigated range and is also applicable to different spectral resolutions making this relation in general useful for deriving effective temperatures in high-extinction regions where photometric temperatures are not reliable.
Context.
The nuclear stellar disc (NSD) is, together with the nuclear star cluster (NSC) and the central massive black hole, one of the main components in the central parts of our Milky Way. However, ...until recently, only a few studies of the stellar content of the NSD have been obtained owing to extreme extinction and stellar crowding.
Aims.
We study the kinematics and global metallicities of the NSD based on the observations of K/M giant stars via a dedicated KMOS (VLT, ESO) spectroscopic survey.
Methods.
We traced radial velocities and metallicities, which were derived based on spectral indices (Na I and CO) along the NSD, and compared those with a Galactic bulge sample of APOGEE (DR16) and data from the NSC.
Results.
We find that the metallicity distribution function and the fraction of metal-rich and metal-poor stars in the NSD are different from the corresponding distributions and ratios of the NSC and the Galactic bulge. By tracing the velocity dispersion as a function of metallicity, we clearly see that the NSD is kinematically cool and that the velocity dispersion decreases with increasing metallicity contrary to the inner bulge sample of APOGEE (|
b
|< 4°). Using molecular gas tracers (H
2
CO, CO(4−3)) of the central molecular zone (CMZ), we find an astonishing agreement between the gas rotation and the rotation of the metal-rich population. This agreement indicates that the metal-rich stars could have formed from gas in the CMZ. On the other hand, the metal-poor stars show a much slower rotation profile with signs of counter-rotation, thereby indicating that these stars have a different origin.
Conclusions.
Coupling kinematics with global metallicities, our results demonstrate that the NSD is chemically and kinematically distinct with respect to the inner bulge, which indicates a different formation scenario.
We present an overview of the distributions of 11 elemental abundances in the Milky Way's (MW) inner regions, as traced by APOGEE stars released as part of the Sloan Digital Sky Survey Data Release ...14/15 (DR14/DR15), including O, Mg, Si, Ca, Cr, Mn, Co, Ni, Na, Al, and K. This sample spans ∼4000 stars with RGC ≤ 4.0 kpc, enabling the most comprehensive study to date of these abundances and their variations within the innermost few kiloparsecs of the MW. We describe the observed abundance patterns (X/Fe-Fe/H), compare to previous literature results and to patterns in stars at the solar Galactocentric radius (RGC), and discuss possible trends with DR14/DR15 effective temperatures. We find that the position of the Mg/Fe-Fe/H "knee" is nearly constant with RGC, indicating a well-mixed star-forming medium or high levels of radial migration in the early inner Galaxy. We quantify the linear correlation between pairs of elements in different subsamples of stars and find that these relationships vary; some abundance correlations are very similar between the -rich and -poor stars, but others differ significantly, suggesting variations in the metallicity dependencies of certain supernova yields. These empirical trends will form the basis for more detailed future explorations and for the refinement of model comparison metrics. That the inner MW abundances appear dominated by a single chemical evolutionary track and that they extend to such high metallicities underscore the unique importance of this part of the Galaxy for constraining the ingredients of chemical evolution modeling and for improving our understanding of the evolution of the Galaxy as a whole.
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