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Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

Bruton tyrosine kinase (BTK) inhibitors can interrupt the crosstalk between follicular lymphoma FL cells and macrophages thereby inducing downregulation of pro-survival pathways in FL cells. Here this group reports a phase 2 single-arm trial evaluating the regimen of acalabrutinib with lenalidomide plus rituximab on twenty four patients with previously untreated FL.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

Antigen escape relapse remains a major obstacle when treating B-cell malignancies with immunotherapies. Here, the authors show that IKAROS regulates the surface expression of CD19 and CD22, revealing a mechanism by which B-cell cancers evade targeted immunotherapies.

Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.

Diffuse large B-cell lymphoma is an aggressive heterogeneous tumour type with poorly understood aetiology. Here, Green et al. show that transient expression of Bcl6in haematopoietic stem cells is sufficient to induce mature B-cell lymphoma, indicating that it acts as a ‘hit-and-run’ oncogene.

EPIC-seq predicts expression of individual genes from cell-free DNA.

Circulating tumor DNA is detected with high sensitivity and specificity using molecular barcoding and in silico error correction.

The sensitivity of circulating tumor DNA detection is improved by identifying sequences with two or more mutations.

The potential use of circulating tumour DNA in classic Hodgkin lymphoma detection, classification and monitoring is defined.

The human germinal centre-associated lymphoma gene is expressed in germinal centre B-lymphocytes; however, its function is unknown. Here the authors show that human germinal centre-associated lymphoma activates Syk kinase, leading to lymphoid hyperplasia and systemic reactive amyloid A amyloidosis in transgenic mice.

Promising results of cancer therapies in transplant tumor models often fail to predict efficacy in clinical trials. Here the authors show that, while transplant tumors are cured by radiotherapy and PD-1 blockade, autochthonous sarcomas are resistant to the identical treatment, recapitulating the immune landscape and resistance to checkpoint blockade observed in most sarcoma patients.

CIBERSORTx, a suite of computational tools, enables inference of cell type abundance and cell-type-specific gene expression profiles from bulk RNA profiles.

A neural network trained on diverse datasets improves prediction of HLA class II epitope presentation.

The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

A searchable pan-cancer resource generated using data from nearly 18,000 human tumors reveals links between tumor infiltration by particular leukocyte subsets, tumor expression of particular gene signatures, and patient prognosis.

A computational method to identify cell types within a complex tissue, based on analysis of gene expression profiles, is described in this paper.

EGFR-mutant non-small cell lung cancer is routinely treated with EGFR inhibitors, although resistance inevitably develops. Here, the authors sequence circulating tumour DNA and show that resistance to the third-generation inhibitor rociletinib is heterogeneous and recurrently involves somatic alterations of MET, EGFR, PIK3CA, ERRB2, and KRAS.

Formaldehyde is universally employed in the fixation of tissue specimens, where it forms adducts with biomolecules, but this hinders the analysis of nucleic acids in the specimen. Bifunctional organocatalysts that speed the reversal of formaldehyde adducts of RNA and DNA are now reported, and show promise for general use in clinical specimens.

In this Perspective, attendees of the Herrenhausen Tumour Heterogeneity meeting discuss the challenges in understanding tumour heterogeneity and propose ways forward for overcoming these hurdles.

Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.

Aaron Newman and his colleagues introduce a next-generation sequencing–based approach for the cost-effective detection and quantitation of tumor-derived circulating DNA in both early- and advanced-stage tumors and with high levels of sensitivity and specificity. CAPP-Seq (cancer personalized profiling by deep sequencing) can simultaneously detect multiple mutations and mutation types, including rearrangements. Here, utility is demonstrated for non–small-cell lung cancer.