We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and ...whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
•Comprehensive molecular analysis is performed on 66 kidney chromophobe cases•Global molecular patterns provide clues as to this cancer’s cell of origin•mtDNA sequencing reveals loss-of-function mutations in NADH dehydrogenase subunits•Genomic structural rearrangements involving TERT promoter region are assessed
Davis et al. describe the landscape of somatic genomic alterations of chromophobe renal cell carcinomas, showing that changes in mitochondrial function are an inherent component of the disease biology and identifying genomic rearrangement as a mechanism for elevated TERT expression.
The Imaging and Medical beamline at the Australian Synchrotron achieved `first light' in December 2008. Here, the first experiments performed on the beamline are reported, which involved both X‐ray ...imaging and tomography studies for a range of samples. The use of a plastic‐edge phantom for quantitative measurements of contrast and resolution proved to be very instructive and helped to confirm certain parameter values such as the effective horizontal source size, detector resolution and average X‐ray energy for the polychromatic beam.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other ...carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.
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•Expanded the somatic genetic landscape of papillary thyroid cancer•Identified new cancer genes and new driver events in known cancer genes.•Signaling signatures and differentiation properties characterized across cohort•Developed a molecular classification of papillary thyroid carcinoma
A TCGA analysis of papillary thyroid carcinoma paints a nearly complete picture of its genomic drivers, reveals intriguing differences between the consequences of mutant BRAF and RAS signaling, and enables development of a scoring and classification scheme that may beneficially alter treatment courses.
Most planetary discoveries with the K2 and Transiting Exoplanet Survey Satellite (TESS) missions are restricted to short periods because of the limited duration of observation. However, the ...re-observation of sky area allows for the detection of longer period planets. We describe new transits detected in six candidate planetary systems that were observed by multiple K2 mission campaigns. One of these systems is a multiplanet system with four candidate planets; we present new period constraints for two planets in this system. In the other five systems, only one transit is observed in each campaign, and we derive period constraints from this new data. The period distributions are highly multimodal resulting from missed potential transits in the gap between observations. Each peak in the distribution corresponds to transits at an integer harmonic of the two observed transits. We further detail a generalized procedure to constrain the period for planets with multiple observations with intervening gaps. Because long-period photometrically discovered planets are rare, these systems are interesting targets for follow-up observations and confirmation. Specifically, all six systems are bright enough (V = 10.4-12.7) to be amenable to radial velocity follow-up. This work serves as a template for period constraints in a host of similar yet-to-be-discovered planets in long baseline, temporally gapped observations conducted by the TESS mission.
There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we ...present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
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•Comprehensive molecular analysis of 333 primary prostate carcinomas•Seven subtypes defined by ETS fusions or mutations in SPOP, FOXA1, and IDH1•Substantial epigenetic heterogeneity, including a hypermethylated IDH1 mutant subset•Presumed actionable lesions in the PI3K, MAPK, and DNA repair pathways
Molecular analysis of 333 primary prostate carcinomas reveals substantial heterogeneity and major subtypes among patients, as well as potentially actionable lesions valuable for clinical management of the disease.
Ground-based, high-resolution spectrographs are providing us with an unprecedented view of the dynamics and chemistry of the atmospheres of planets outside the Solar System. While there are a large ...number of stable and precise high-resolution spectrographs on modest-size telescopes, it is the spectrographs at observatories with apertures larger than 3.5 m that dominate the atmospheric follow-up of exoplanets. In this work we explore the potential of characterising exoplanetary atmospheres with FIES, a high-resolution spectrograph at the 2.56 m Nordic Optical Telescope. We observed two transits of MASCARA-2 b (also known as KELT-20 b) and one transit of KELT-9 b to search for atomic iron, a species that has recently been discovered in both neutral and ionised forms in the atmospheres of these ultra-hot Jupiters using large telescopes. Using a cross-correlation method, we detect a signal of FeII at the 4.5and 4.0level in the transits of MaSCARA-2 b. We also detect FeII in the transit of KELT-9 b at the 8.5level. Although we do not find any significant Doppler shift in the signal of MASCARA-2 b, we do measure a moderate blueshift (3a-6 km s1) of the feature in KELT-9 b, which might be a manifestation of high-velocity winds transporting FeII from the planetary dayside to the nightside. Our work demonstrates the feasibility of investigating exoplanet atmospheres with FIES, and it potentially unlocks a wealth of additional atmosphere detections with this and other high-resolution spectrographs mounted on similar-size telescopes.
Abstract
Convergent disk migration has long been suspected to be responsible for forming planetary systems with a chain of mean-motion resonances (MMRs). Dynamical evolution over time could disrupt ...the delicate resonant configuration. We present TOI-1136, a 700 ± 150 Myr old G star hosting at least six transiting planets between ∼2 and 5
R
⊕
. The orbital period ratios deviate from exact commensurability by only 10
−4
, smaller than the ∼10
−2
deviations seen in typical Kepler near-resonant systems. A transit-timing analysis measured the masses of the planets (3–8
M
⊕
) and demonstrated that the planets in TOI-1136 are in true resonances with librating resonant angles. Based on a Rossiter–McLaughlin measurement of planet d, the star’s rotation appears to be aligned with the planetary orbital planes. The well-aligned planetary system and the lack of a detected binary companion together suggest that TOI-1136's resonant chain formed in an isolated, quiescent disk with no stellar flyby, disk warp, or significant axial asymmetry. With period ratios near 3:2, 2:1, 3:2, 7:5, and 3:2, TOI-1136 is the first known resonant chain involving a second-order MMR (7:5) between two first-order MMRs. The formation of the delicate 7:5 resonance places strong constraints on the system’s migration history. Short-scale (starting from ∼0.1 au) Type-I migration with an inner disk edge is most consistent with the formation of TOI-1136. A low disk surface density (Σ
1 au
≲ 10
3
g cm
−2
; lower than the minimum-mass solar nebula) and the resultant slower migration rate likely facilitated the formation of the 7:5 second-order MMR.
Ground-based, high-resolution spectrographs are providing us with an unprecedented view of the dynamics and chemistry of the atmospheres of planets outside the Solar System. While there are a large ...number of stable and precise high-resolution spectrographs on modest-size telescopes, it is the spectrographs at observatories with apertures larger than 3.5 m that dominate the atmospheric follow-up of exoplanets. In this work we explore the potential of characterising exoplanetary atmospheres with FIES, a high-resolution spectrograph at the 2.56 m Nordic Optical Telescope. We observed two transits of MASCARA-2 b (also known as KELT-20 b) and one transit of KELT-9 b to search for atomic iron, a species that has recently been discovered in both neutral and ionised forms in the atmospheres of these ultra-hot Jupiters using large telescopes. Using a cross-correlation method, we detect a signal of Fe
II
at the 4.5
σ
and
4.0σ
level in the transits of MaSCARA-2 b. We also detect Fe
II
in the transit of KELT-9 b at the 8.5
σ
level. Although we do not find any significant Doppler shift in the signal of MASCARA-2 b, we do measure a moderate blueshift (3–6 km s
−1
) of the feature in KELT-9 b, which might be a manifestation of high-velocity winds transporting Fe
II
from the planetary dayside to the nightside. Our work demonstrates the feasibility of investigating exoplanet atmospheres with FIES, and it potentially unlocks a wealth of additional atmosphere detections with this and other high-resolution spectrographs mounted on similar-size telescopes.
Abstract
We present a near-infrared transmission spectrum of the long-period (
P
= 542 days), temperate (
T
eq
= 294 K) giant planet HIP 41378 f obtained with the Wide-Field Camera 3 instrument ...aboard the Hubble Space Telescope (HST). With a measured mass of 12 ± 3
M
⊕
and a radius of 9.2 ± 0.1
R
⊕
, HIP 41378 f has an extremely low bulk density (0.09 ± 0.02 g cm
−3
). We measure the transit depth with a median precision of 84 ppm in 30 spectrophotometric channels with uniformly sized widths of 0.018
μ
m. Within this level of precision, the spectrum shows no evidence of absorption from gaseous molecular features between 1.1 and 1.7
μ
m. Comparing the observed transmission spectrum to a suite of 1D radiative-convective-thermochemical-equilibrium forward models, we rule out clear, low-metallicity atmospheres and find that the data prefer high-metallicity atmospheres or models with an additional opacity source, such as high-altitude hazes and/or circumplanetary rings. We explore the ringed scenario for HIP 41378 f further by jointly fitting the K2 and HST light curves to constrain the properties of putative rings. We also assess the possibility of distinguishing between hazy, ringed, and high-metallicity scenarios at longer wavelengths with the James Webb Space Telescope. HIP 41378 f provides a rare opportunity to probe the atmospheric composition of a cool giant planet spanning the gap in temperature, orbital separation, and stellar irradiation between the solar system giants, directly imaged planets, and the highly irradiated hot Jupiters traditionally studied via transit spectroscopy.
Abstract
The Kepler and TESS missions have demonstrated that planets are ubiquitous. However, the success of these missions heavily depends on ground-based radial velocity (RV) surveys, which ...combined with transit photometry can yield bulk densities and orbital properties. While most Kepler host stars are too faint for detailed follow-up observations, TESS is detecting planets orbiting nearby bright stars that are more amenable to RV characterization. Here, we introduce the TESS-Keck Survey (TKS), an RV program using ∼100 nights on Keck/HIRES to study exoplanets identified by TESS. The primary survey aims are investigating the link between stellar properties and the compositions of small planets; studying how the diversity of system architectures depends on dynamical configurations or planet multiplicity; identifying prime candidates for atmospheric studies with JWST; and understanding the role of stellar evolution in shaping planetary systems. We present a fully automated target selection algorithm, which yielded 103 planets in 86 systems for the final TKS sample. Most TKS hosts are inactive, solar-like, main-sequence stars (4500 K ≤
T
eff
<6000 K) at a wide range of metallicities. The selected TKS sample contains 71 small planets (
R
p
≤ 4
R
⊕
), 11 systems with multiple transiting candidates, six sub-day-period planets and three planets that are in or near the habitable zone (
S
inc
≤ 10
S
⊕
) of their host star. The target selection described here will facilitate the comparison of measured planet masses, densities, and eccentricities to predictions from planet population models. Our target selection software is publicly available and can be adapted for any survey that requires a balance of multiple science interests within a given telescope allocation.
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