Circulating Tumor DNA as a Marker of Recurrence Risk in Stage III Colorectal Cancer: The α-CORRECT Study.

Background And Objectives: Identification of colorectal cancer (CRC) patients at high risk of recurrence could be of substantial clinical use. We evaluated the association of ctDNA status, using a tumor-informed assay, with recurrence-free survival (RFS).

Methods: Stage III CRC patients were enrolled between 2016 and 2020.

The genome sequence of an alderfly, Pictet, 1836.

We present a genome assembly from an individual female (alderfly; Arthropoda; Insecta; Megaloptera; Sialidae). The genome sequence is 392.1 megabases in span.

The genome sequence of a green lacewing, (Scopoli, 1763).

We present a genome assembly from an individual (green lacewing; Arthropoda; Insecta; Neuroptera; Chrysopidae). The genome sequence spans 732.30 megabases.

The genome sequence of the Common Alderfly, (Linnaeus, 1758).

We present a genome assembly from an individual (alderfly; Arthropoda; Insecta; Megaloptera; Sialidae). The genome sequence is 462.0 megabases in span.

Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult.

Associations with other cancer-related biomarkers might contribute to poor outcomes in RAS-altered, younger patients with colorectal cancer.

Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.

Value of next generation sequencing (NGS) testing in advanced cancer patients.

Objective: The availability of targeted therapies for oncology patients is increasing. Available genomic tests to identify treatment-eligible patients include single gene tests and gene panel tests, including the whole-exome, whole-transcriptome OncoExTra test. We assessed the costs and clinical benefits of test choice.

Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult.

Comprehensive Review on the Clinical Impact of Next-Generation Sequencing Tests for the Management of Advanced Cancer.

Purpose: This review summarizes the published evidence on the clinical impact of using next-generation sequencing (NGS) tests to guide management of patients with cancer in the United States.

Methods: We performed a comprehensive literature review to identify recent English language publications that presented progression-free survival (PFS) and overall survival (OS) of patients with advanced cancer receiving NGS testing.

Results: Among 6,475 publications identified, 31 evaluated PFS and OS among subgroups of patients who received NGS-informed cancer management.

Tumor-Type Agnostic, Targeted Therapies: BRAF Inhibitors Join the Group.

In the present review, we briefly discuss the breakthrough advances in precision medicine using a tumor-agnostic approach and focus on BRAF treatment modalities, the mechanisms of resistance and the diagnostic approach in cancers with BRAF mutations. Tumor-type agnostic drug therapies work across cancer types and present a significant novel shift in precision cancer medicine. They are the consequence of carefully designed clinical trials that showed the value of tumor biomarkers, not just in diagnosis but in therapy guidance.

The 17-gene Genomic Prostate Score assay as a predictor of biochemical recurrence in men with intermediate and high-risk prostate cancer.

The validated 17-gene Oncotype DX Genomic Prostate Score® (GPS™) assay risk-stratifies prostate-cancer patients with localized disease. The assay has primarily been utilized in lower risk patients deciding between active surveillance versus definitive therapy. In this retrospective cohort study, we analyze the association of the GPS result with time to biochemical recurrence post-prostatectomy in patients with National Comprehensive Cancer Network® (NCCN) intermediate and higher risk prostate cancer.

Genome Assembly of the Ty1-Less Saccharomyces paradoxus Strain DG1768.

Here, we report an essentially complete genome assembly for the Ty1-less Saccharomyces paradoxus strain DG1768 (derivative of strain 337) based on PacBio and Illumina shotgun sequence data. We also document the genetic alterations that make this yeast strain a key resource for Ty1 mobility studies.

A genome assembly and the somatic genetic and epigenetic mutation rate in a wild long-lived perennial Populus trichocarpa.

Background: Plants can transmit somatic mutations and epimutations to offspring, which in turn can affect fitness. Knowledge of the rate at which these variations arise is necessary to understand how plant development contributes to local adaption in an ecoevolutionary context, particularly in long-lived perennials.

Results: Here, we generate a new high-quality reference genome from the oldest branch of a wild Populus trichocarpa tree with two dominant stems which have been evolving independently for 330 years.

Fitness consequences of a non-recombining drive chromosome can explain its prevalence in the wild.

Understanding the pleiotropic consequences of gene drive systems on host fitness is essential to predict their spread through a host population. Here, we study (SR) X-chromosome drive in the fly , where SR causes the death of Y-bearing sperm in male carriers. SR males only sire daughters, which all carry SR, thus giving the chromosome a transmission advantage.

Firefly genomes illuminate parallel origins of bioluminescence in beetles.

Fireflies and their luminous courtships have inspired centuries of scientific study. Today firefly luciferase is widely used in biotechnology, but the evolutionary origin of bioluminescence within beetles remains unclear. To shed light on this long-standing question, we sequenced the genomes of two firefly species that diverged over 100 million-years-ago: the North American and Japanese To compare bioluminescent origins, we also sequenced the genome of a related click beetle, the Caribbean , with bioluminescent biochemistry near-identical to fireflies, but anatomically unique light organs, suggesting the intriguing hypothesis of parallel gains of bioluminescence.

Molecular variation across populations of a widespread North American firefly, Photinus pyralis, reveals that coding changes do not underlie flash color variation or associated visual sensitivity.

Background: Genes underlying signal production and reception are expected to evolve to maximize signal detection in specific environments. Fireflies vary in their light signal color both within and between species, and thus provide an excellent system in which to study signal production and reception in the context of signaling environments. Differences in signal color have been hypothesized to be due to variation in the sequence of luciferase, the enzyme that catalyzes the light reaction.

The evolution of sexual signal modes and associated sensor morphology in fireflies (Lampyridae, Coleoptera).

Animals employ different sexual signal modes (e.g. visual, acoustic, chemical) in different environments and behavioural contexts.

Modeling the Evolution of Female Meiotic Drive in Maize.

Autosomal drivers violate Mendel's law of segregation in that they are overrepresented in gametes of heterozygous parents. For drivers to be polymorphic within populations rather than fixing, their transmission advantage must be offset by deleterious effects on other fitness components. In this paper, we develop an analytical model for the evolution of autosomal drivers that is motivated by the neocentromere drive system found in maize.

Fitness Costs and Variation in Transmission Distortion Associated with the Abnormal Chromosome 10 Meiotic Drive System in Maize.

Meiotic drive describes a process whereby selfish genetic elements are transmitted at levels greater than Mendelian expectations. Maize abnormal chromosome 10 (Ab10) encodes a meiotic drive system that exhibits strong preferential segregation through female gametes. We performed transmission assays on nine Ab10 chromosomes from landraces and teosinte lines and found a transmission advantage of 62-79% in heterozygotes.

Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation.

Background: Differences in DNA methylation can arise as epialleles, which are loci that differ in chromatin state and are inherited over generations. Epialleles offer an additional source of variation that can affect phenotypic diversity beyond changes to nucleotide sequence. Previous research has looked at the rate at which spontaneous epialleles arise but it is currently unknown how they are maintained across generations.

Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90.

The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. The potential for Hsp90 and other putative buffers to increase robustness to mutation has had major impact on disease models, quantitative genetics, and evolutionary theory. But Hsp90 sometimes contradicts expectations for a buffer by potentiating rapid phenotypic changes that would otherwise not occur.

Selection on Position of Nonsense Codons in Introns.

Introns occasionally remain in mature messenger RNAs (mRNAs) due to splicing errors and the translated, aberrant proteins that result represent a metabolic cost and may have other deleterious consequences. The nonsense-mediated decay (NMD) pathway degrades aberrant mRNAs, which it recognizes by the presence of an in-frame premature termination codon (PTC). We investigated whether selection has shaped the location of PTCs in introns to reduce waste and facilitate NMD.

The evolution of adult light emission color in North American fireflies.

Firefly species (Lampyridae) vary in the color of their adult bioluminescence. It has been hypothesized that color is selected to enhance detection by conspecifics. One mechanism to improve visibility of the signal is to increase contrast against ambient light.

The repeatability of genome-wide mutation rate and spectrum estimates.

Over the last decade, mutation studies have grown in popularity due to the affordability and accessibility of whole genome sequencing. As the number of species in which spontaneous mutation has been directly estimated approaches 20 across two domains of life, questions arise over the repeatability of results in such experiments. Five species were identified in which duplicate mutation studies have been performed.