Cancer genetics articles within Nature Communications

Featured

  • Article
    | Open Access

    Rare tumour specific mutations in patient samples act as markers to monitor the course of disease. Here the authors report superRCA assays for rapid, highly specific detection of DNA sequence variants present at very low frequencies in DNA samples with flow cytometry readout; they use this on AML patients.

    • Lei Chen
    • , Anna Eriksson
    •  & Ulf Landegren

  • Article
    | Open Access

    Few genetic biomarkers are known for cancer immunotherapy. Here the authors identify recurrently-mutated genes and pathways associated with treatment response and develop a classifier using tumour whole exome sequencing and clinical features.

    • Zoran Z. Gajic
    • , Aditya Deshpande
    •  & Neville E. Sanjana

  • Article
    | Open Access

    Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk.

    • Philip S. Robinson
    • , Laura E. Thomas
    •  & Michael R. Stratton

  • Article
    | Open Access

    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.

    • Josh N. Vo
    • , Yi-Mi Wu
    •  & Arul M. Chinnaiyan

  • Article
    | Open Access

    The impact of germline variants on somatic alterations in cancer remains to be explored in large-scale datasets. Here, the authors study the association of rare germline variants with somatic mutational processes in more than 15,000 tumors, and reveal that damaging variants in newly-identifed genes are prevalent in the population.

    • Mischan Vali-Pour
    • , Solip Park
    •  & Fran Supek

  • Article
    | Open Access

    Here the authors show mutation of the BAF chromatin remodeler subunit ARID1A results in an ARID1B-dependent upregulation of HERVH, an ERV required for the pluripotency regulatory network. These HERVH RNAs can partition into BRD4 foci, affecting BRD4-dependent transcription. Suppression of HERVH in colorectal cancer cells and patient-derived organoids impairs tumor growth.

    • Chunhong Yu
    • , Xiaoyun Lei
    •  & Kai Yuan

  • Article
    | Open Access

    Long-read sequencing technologies are useful for the multifaceted task of characterising somatic mutations, including structural variants, in cancers. Here, the authors combine short and long read sequencing for the phasing analysis, which enables them to resolve the chromosomal backgrounds of somatic mutations in Japanese non-small cell lung cancers.

    • Yoshitaka Sakamoto
    • , Shuhei Miyake
    •  & Ayako Suzuki

  • Article
    | Open Access

    Germline biallelic pathogenic MUTYH variants predispose patients to colorectal cancer (CRC); however, approaches to identify MUTYH variant carriers are lacking. Here, the authors evaluated mutational signatures that could distinguish MUTYH carriers in large CRC cohorts, and found MUTYH-associated somatic mutations.

    • Peter Georgeson
    • , Tabitha A. Harrison
    •  & Daniel D. Buchanan

  • Article
    | Open Access

    Androgen receptor can promote tumour progression in desmoplastic small round cell tumour (DSRCT), an aggressive paediatric malignancy that predominantly affects young males. Here, the authors show that DSRCT is an AR-driven malignancy and sensitive to androgen deprivation therapy

    • Salah-Eddine Lamhamedi-Cherradi
    • , Mayinuer Maitituoheti
    •  & Joseph A. Ludwig

  • Article
    | Open Access

    It is unclear whether somatic mutation rates are elevated in Lynch Syndrome (LS), which is the most common cause of hereditary colorectal cancer. Here, the authors use whole-genome sequencing and organoid cultures to show that normal tissues in LS patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution.

    • Bernard C. H. Lee
    • , Philip S. Robinson
    •  & Michael R. Stratton

  • Article
    | Open Access

    Mitochondrial metabolism has been associated with tumourigenesis in acute myeloid leukaemia (AML) and currently considered as a potential therapeutic target. Here, the authors show, in patients with AML, that germline mutations in mitochondrial complex I are mutually exclusive with somatic mutations in the metabolic enzyme IDH1, and find IDH1 mutant cells have increased sensitivity to complex I inhibitors.

    • Mahmoud A. Bassal
    • , Saumya E. Samaraweera
    •  & Richard J. D’Andrea

  • Article
    | Open Access

    Astroblastoma (AB) is an uncommon brain tumour and its origin remains unknown. Here, the authors perform integrative molecular analysis of 35 AB-like tumours and provide evidence that these arise in the context of epigenetic and genetic changes in neural progenitors occurring during brain development.

    • Norman L. Lehman
    • , Nathalie Spassky
    •  & Akshitkumar M. Mistry

  • Article
    | Open Access

    Mutations of ESR1, the gene encoding the estrogen receptor alpha, are associated with acquired resistance to therapy in luminalbreast cancer. Here the authors show that ESR1 mutant tumors gain basal-like features with increased expression of basal cytokeratines and immune activation.

    • Zheqi Li
    • , Olivia McGinn
    •  & Steffi Oesterreich

  • Article
    | Open Access

    The effect of hyaluronan-mediated motility receptor (HMMR) expression in BRCA1-associated breast cancer risk remains unknown. Here, HMMR overexpression induces the activation of cGAS-STING and non-canonical NF-κB signalling, instigating an immune permissive environment for breast cancer development.

    • Francesca Mateo
    • , Zhengcheng He
    •  & Miquel Angel Pujana

  • Article
    | Open Access

    Clonal dynamics and selection have not been fully understood in patient-derived xenografts (PDX) of acute myeloid leukemia (AML). Here, the authors generate 160 AML-PDX models to track the clonal dynamics of primary and relapsed AML, and find selectively enriched subclones that are associated with resistance to therapy.

    • Naomi Kawashima
    • , Yuichi Ishikawa
    •  & Hitoshi Kiyoi

  • Article
    | Open Access

    Loss of the tumour suppressor gene PTEN leads to the activation of pro-tumourigenic signalling pathways. Here, the authors analyse sequencing data from a large cohort of colorectal cancer patients harbouring PTEN mutations and identify distinct patterns of associations with genomic and clinical features.

    • Ilya G. Serebriiskii
    • , Valery Pavlov
    •  & Erica A. Golemis

  • Article
    | Open Access

    DNA damage repair genes have been linked with increased aggressiveness of prostate cancer, however, the extent of mutation of these genes has not been analyzed within a cohort of African American patients. Here, the authors identify increased mutation rates in specific DNA repair genes, compared with prostate cancer patients with European Ancestry.

    • Indu Kohaar
    • , Xijun Zhang
    •  & Gyorgy Petrovics

  • Article
    | Open Access

    Numerous rationally-designed and directed-evolution variants of SpCas9 have been reported to expand the utility of CRISPR technology. Here the authors make comparisons of numerous Cas9 variants, nominate options for base editing screens with denser coverage with A>G and C>T base editing screens and identify loss-of-function mutations in BRCA1 and Venetoclax-resistant mutations in BCL2.

    • Annabel K. Sangree
    • , Audrey L. Griffith
    •  & John G. Doench

  • Article
    | Open Access

    Germline variants that predispose to lung cancer have been mostly studied in Western populations, but data from Chinese patients is lacking. Here the authors analyze lung cancer germline variants in 1794 Chinese patients, finding exclusive variants or with different frequency compared to TCGA data.

    • Wenying Peng
    • , Bin Li
    •  & Lin Wu

  • Article
    | Open Access

    The interpretation of somatic variants in cancer is challenging due to the scale and complexity of sequencing data. Here, the authors present PORI, an open-source framework for interpreting somatic variants in cancer using graph knowledge base tools, automated reporting, and manual curation.

    • Caralyn Reisle
    • , Laura M. Williamson
    •  & Steven J. M. Jones

  • Article
    | Open Access

    Most ovarian cancers originate from cells originally derived from Müllerian Duct cells. Here, the authors show that the methylation profile of Müllerian Duct cells isolated from cervical samples can predict whether a woman has cervical cancer.

    • James E. Barrett
    • , Allison Jones
    •  & Martin Widschwendter

  • Article
    | Open Access

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that modulates target gene expression in response to changes in oxygen availability. Here the authors show that HIF-1 forms a complex with TRIM28 and DNA-dependent protein kinase (DNA-PK) that phosphorylates TRIM28. This leads to CDK9 recruitment, which stimulates RNA polymerase II (RNAPII) pause release and transcriptional elongation.

    • Yongkang Yang
    • , Haiquan Lu
    •  & Gregg L. Semenza

  • Article
    | Open Access

    Replication stress and abundant repetitive sequences have emerged as primary conditions underlying genomic instability in eukaryotes. Here the authors use a prokaryotic Tus/Ter barrier designed to induce transient replication fork stalling near inverted repeats in the budding yeast genome to support a model for recombination of closely linked repeats at stalled replication forks.

    • Léa Marie
    •  & Lorraine S. Symington

  • Article
    | Open Access

    The causality and functional roles of disease-associated variants revealed by genome-wide association studies (GWAS) are mostly unexplored. Here the authors identify putative causal variants in multiple myeloma and find their association with gene expression and chromatin accessibility.

    • Ram Ajore
    • , Abhishek Niroula
    •  & Björn Nilsson

  • Article
    | Open Access

    High tumour heterogeneity hinders the identification of molecular subtypes in prostate cancer. Here, the authors integrate single-cell chromatin accessibility data with multiplex imaging and reveal distinct chromatin features and transcriptional factor binding signatures in high- and low-grade prostate tumours.

    • Sebnem Ece Eksi
    • , Alex Chitsazan
    •  & Andrew C. Adey

  • Article
    | Open Access

    In the classic two-hit model, both alleles of a tumour suppressor gene need to be inactivated in order to promote cancer. Here, the authors challenge this model, finding that many cancer genes can be either one-hit or two-hit drivers depending on the context and other mutations in a tumor.

    • Solip Park
    • , Fran Supek
    •  & Ben Lehner

  • Article
    | Open Access

    Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.

    • Olusegun Isaac Alatise
    • , Gregory C. Knapp
    •  & T. Peter Kingham

  • Article
    | Open Access

    The impact of genetic fusions on degrons, which are motifs for ubiquitin-mediated protein degradation, has not been fully explored. Here, the authors analyse fusion genes affecting degrons in pan-cancer genomics data, validate their functional impact and find enrichment for both internal and C-terminal degron losses.

    • Jing Liu
    • , Collin Tokheim
    •  & Wenyi Wei

  • Article
    | Open Access

    The tumor suppressor BRCA2 protects stalled DNA replication forks from unrestrained degradation; however the mechanism whereby unprotected stalled forks are preserved and restarted has remained elusive. Here the authors show that the WRN helicase promotes stalled fork recovery and limits fork hyper-degradation in the absence of BRCA2 protection.

    • Arindam Datta
    • , Kajal Biswas
    •  & Robert M. Brosh Jr

  • Article
    | Open Access

    TET2 mutations are frequent in myeloid malignancies and in elderly individuals with or without cytopenia. Here, the authors analyse the association between TET2 mutations and methylation changes in healthy elderly twins and patients with cytopenia and compare them to those from leukemia.

    • Morten Tulstrup
    • , Mette Soerensen
    •  & Kirsten Grønbæk

  • Article
    | Open Access

    Understanding the frequency of gene mutations in cancer could be important for generating targeted therapeutics. Here, the authors use SEER data and cancer genomics data from TCGA to estimate the gene mutation frequencies in the US cancer population.

    • Gaurav Mendiratta
    • , Eugene Ke
    •  & Edward C. Stites

  • Article
    | Open Access

    Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

    • Aida Ferreiro-Iglesias
    • , James D. McKay
    •  & Paul Brennan

  • Article
    | Open Access

    Retinoblastoma is the most frequent intraocular paediatric malignancy whose molecular basis remains poorly understood. Here, the authors perform multi-omic analysis and identify two subtypes; one in a cone differentiated state and one more aggressive showing cone dedifferentiation and expressing neuronal markers.

    • Jing Liu
    • , Daniela Ottaviani
    •  & François Radvanyi

  • Article
    | Open Access

    Many factors have been associated with chromosomal damage, including mechanical forces in a constrained cellular environment. Here the authors reveal an association between parity and chromosomal damage by analysing karyotypes of 1946 uterine leiomyomas.

    • Heli Kuisma
    • , Simona Bramante
    •  & Lauri A. Aaltonen

  • Article
    | Open Access

    The identification of transcription factors (TFs) whose binding sites are affected by risk genetic variants remains crucial. Here, the authors develop a statistical framework to analyse ChIP-seq and GWAS data, identify 22 breast cancer risk-associated TFs and a core TF-transcriptional network for FOXA1 and co-factors.

    • Wanqing Wen
    • , Zhishan Chen
    •  & Xingyi Guo

  • Article
    | Open Access

    Chimeric antigen receptor T cells in the clinic currently target cell-type-specific extracellular antigens on malignant cells. Here, authors engineer tumor-specific chimeric antigen receptor T cells that target human leukocyte antigen-presented neoantigens derived from mutant intracellular proteins.

    • Michael S. Hwang
    • , Michelle S. Miller
    •  & Sandra B. Gabelli

  • Article
    | Open Access

    Plasmablastic lymphoma (PBL) is an aggressive lymphoma subtype characterized by poor prognosis but the molecular knowledge of the disease is limited. Here, the authors perform whole exome sequencing and copy number determination of primary samples highlighting IRF4 and JAK-STAT pathways as therapeutic targets for PBL.

    • Fabian Frontzek
    • , Annette M. Staiger
    •  & Georg Lenz

  • Article
    | Open Access

    The BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex is well known to play a fundamental role in DNA repair, but how the complex recruitment is regulated is still a matter of interest. Here the authors reveal mechanistic insights into RNF168 activity being responsible for PALB2 recruitment, through BARD1-BRCA1 during homologous recombination repair.

    • John J. Krais
    • , Yifan Wang
    •  & Neil Johnson

Browse broader subjects

Browse narrower subjects

Browse Cancer genetics across other nature.com journals