Volume 52 Issue 2, February 2020

Huntington’s disease is a severe progressive neurological disorder caused by a CAG-repeat expansion in the HTT gene. A small molecule shows therapeutic potential by inducing contraction of these expanded CAG repeats in cell and mouse models of the disease.

Experiments in developing human erythroid cells show that LIN28B controls hemoglobin switching by directly suppressing BCL11A translation, independently of its role in regulating let-7 microRNA biogenesis.

Naphthyridine-azaquinolone specifically binds slipped-CAG DNA intermediates, induces contractions of expanded repeats and reduces mutant HTT protein aggregates in cell and animal models of Huntington’s disease.

Multitrait genome-wide analysis of glaucoma and related phenotypes identifies new risk loci and enables development of a polygenic risk score to predict disease susceptibility and key clinical outcomes.

Genome-wide association analysis of 1,172 urinary metabolites identifies 240 metabolite–locus associations that when combined with UK Biobank data suggest novel metabolic mediators of disease and markers of disease risk.

Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

ARID1A and other SWI/SNF components are critical for response to estrogen-receptor antagonists in breast cancer. SWI/SNF-specific gene knockouts lead to drug resistance and ARID1A mutations are more frequent in resistant tumors from patients.

A CRISPR–CAS9 screen, analysis of patient data, and functional in vivo and in vitro experiments identify a critical role for ARID1A in determining breast luminal cell identity and endocrine therapeutic response in estrogen-receptor-positive breast cancer.

MutPanning is a new method to detect cancer driver genes that identifies genes with an excess of mutations in unusual nucleotide contexts. Applying this to whole-exome sequencing data from 11,873 tumor–normal pairs identifies 460 driver genes.

A mouse model that combines nitrosamide exposure with inducible, tissue-specific TP53 alterations is used to generate premalignant gastric organoids and provides insights into the development of gastric premalignancy.

Whole-genome sequencing, transcriptome sequencing and single-cell analysis of primary and metastatic pancreatic adenocarcinoma identify molecular subtypes and intratumor heterogeneity.