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The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Clinical exome and transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site, as part of the Michigan Oncology Sequencing (MI-ONCOSEQ) Program.

Arul Chinnaiyan and colleagues identify NAB2-STAT6 fusions in 52 of 52 solitary fibrous tumor cases. Overexpression of this fusion induced cell proliferation, which could be suppressed by knockdown of EGR1.

Arul Chinnaiyan and colleagues report the results of prospective clinical sequencing of 11 estrogen receptor–positive metastatic breast cancers. They identify ESR1 mutations affecting the ligand-binding domain in six hormone-resistant metastatic breast cancers and show that the mutant estrogen receptors are constitutively active and continue to be responsive to anti-estrogen therapies in vitro.

Chinnaiyan and colleagues perform a high-throughput compound screen and identify PIKfyve inhibition as a therapeutic strategy to enhance immune checkpoint blockade responses in advanced prostate cancer.

Arul Chinnaiyan and colleagues report that the long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers and predicts poor outcome. Mechanistically, they show that SChLAP1 promotes invasiveness and metastasis and antagonizes the functions of the SWI/SNF chromatin-remodeling complex.

Small-molecule compounds that target the BET domain in proteins such as BRD4 have recently been identified as potential anticancer agents; here, the efficacy of the BRD4-targeting compound JQ1 is demonstrated in castration-resistant prostate cancer driven by deregulated androgen receptor action.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Arul Chinnaiyan and colleagues report the curation of 7,256 RNA sequencing libraries from tumors, normal tissues and cell lines. They find 58,648 lncRNAs, of which 79% are previously unnannotated.

The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.

LncRNAs have been associated with cancer. Here, the authors carry out a systematic review of lncRNAs in breast cancer and show that DSCAM-AS1is highly expressed in oestrogen receptor positive tumours and enhances cancer through an interaction with hnRNPL; and is also associated with tamoxifen resistance.

Chandan Kumar-Sinha and Arul Chinnaiyan summarize the increasing use of sequencing panels to screen for cancer-associated genes in tumor and germline samples. The authors highlight the increasing appreciation of aberrations in regulatory genes or chromatin-related genes and argue that precision oncology must be considered in the context of adding value to the standard of care, not apart from it.

ARLNC1 is a newly discovered lncRNA that is induced by androgen receptor (AR) and maintains AR signaling by stabilizing the AR transcript. Knockdown of ARLNC1 suppresses AR expression, AR signaling and prostate cancer growth in vitro and in vivo.

Myeloid cell subsets are playing important roles in antitumour immunity, and genes affecting their functions are potential targets for immunotherapy. Here authors show that genomic deletion of Pikfyve in CD11c⁺ cells results in tumour growth inhibition via enhanced antigen presentation and priming of antigen-specific CD8⁺ T cells in a mouse tumor model.

SPOP functions as a tumour suppressor in prostate cancer but how the protein is regulated is unclear. Here, the authors identify G3BP1 as a competitive inhibitor of SPOP and show that G3BP1-SPOP axis activates androgen signalling to drive tumorigenesis.

A massive international effort has yielded multifaceted studies of more than 2,600 tumours from 38 tissues, generating a wealth of insights into the genetic basis of cancer.

A transcriptome can be readily assembled from RNA-Seq data in the absence of a reference genome.

Using a combination of new generation long- and short-read sequencing technologies, this study analyses cancer samples for gene fusion transcripts. The approach uncovers transcripts arising from known gene fusions in leukaemia and prostate cancer, as well as newly discovered ones in prostate cancer.

Whole-genome bisulfite sequencing along with whole-genome and transcriptome sequencing of 100 prostate cancer metastases identifies genomic regions that are differentially methylated during disease progression and a novel epigenomic subtype.

Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours of multiple cancer types in mouse models.

New noncoding RNAs can be discovered by assembling transcripts from RNA-Seq data. Prensner et al. apply this approach across >100 prostate cancer samples to find noncoding RNAs that distinguish localized tumors from benign forms of the disease.

CRISPR screen identifies coactivators of the androgen receptor (AR) complex, including NSD2. NSD2 contributes to AR cistrome reprogramming during prostate cancer progression, and its degradation via a novel PROTAC reduces prostate cancer cell viability in vitro.

Recently characterized IDH1 and IDH2 mutations in leukemia and glioblastoma have introduced a fascinating cancer-specific role for metabolic genes essential to cellular respiration. Studies also link aberrant IDH1 and IDH2 activity to an altered metabolite profile, an observation that may have broad implications for both cancer epigenetics and clinical management of disease.

Gene fusions have long been known to have an important role in leukaemias, but they have recently been identified in a majority of prostate cancers. Understanding their role in this disease could lead to better targeted therapies.

Exome sequencing is used to investigate the role of mutations and copy number aberrations in metastatic castration-resistant prostate cancer, revealing recurrent mutations in multiple chromatin/histone modifying genes, as well as genes involved in androgen signalling.

This report identifies oncogenic fusions in individuals with breast cancer involving the genes encoding NOTCH and MAST, recurring in approximately 5–7% of studied cases. The fusions show growth-promoting properties that suggest that they may represent targetable events in a subset of people with breast cancer.

While it is known that localised prostate cancer is characterised by clonal heterogeneity, the clonal origin of synchronous lymph node (LN) metastases remains poorly understood. Here, the authors analyse the clonal origin of LN metastases in prostate cancer patients using multi-region sequencing.

Squamous cell carcinoma of the head and neck often becomes resistant to treatment. In this study, Banerjee et al. show that the ATPase TRIP13 can mediate resistance in cells from these tumours by inducing error prone non-homologous end joining DNA repair.

PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.

Polycomb group proteins are epigenetic gene silencers that are thought to exist in two biochemically distinct multiprotein complexes, termed PRC-1 and -2. Here, Cao et al.show that EED, a core component of PRC2, interacts with and functions as part of PRC1, thus coordinating the activities of both complexes.

Argonaute 2 (AGO2) binds RAS and is required for cellular transformation. Here, the authors establish a KRAS-driven mouse model of pancreatic cancer with conditional loss of AGO2 and show that the early phase of neoplastic lesion initiation is dependent on EGFR/RAS but not AGO2, while AGO2 is required for pancreatic ductal adenocarcinoma progression and metastasis.

Perineural invasion occurs in many head and neck cancers and is thought to be an active process where tumour cells degrade the neural sheath. Here the authors show that the neuropeptide galanin mediates the crosstalk between nerves and cancer cells to promote malignant progression.

Non-small cell lung cancers (NSCLC) that harbour mutations in KRas can be separated into KRas-dependent and -independent subsets. By analysing transcriptome, proteome and phosphoproteome data from NSCLC cell lines, Balbin et al. show that KRas-dependent cell lines activate the Lck pathway.

Dual sequencing of the epigenome and genome could have broad implications in oncology.

Targeted cancer therapy requires knowledge of driver aberrations. Here the authors perform large-scale transcriptome analysis, and show that gene fusions in NRG1, NF1and Hippo pathway genes are recurrent mostly among lung cancers lacking known driver mutations.