Is this you? As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.
Claim your profile
Articles by Sam Behjati
Embryonic origin of cancer in newborn twins
Abstract Studying monozygotic twins who present with identical cancers informs on the developmental origins of childhood tumours. Here, we perform whole genome sequencing on multiple tumour, normal, and placental samples to reconstruct the phylogeny of a soft tissue cancer that spread in utero between monozygotic twins. We demonstrate the origin of the tumour from one twin and time its diversification and transplacental spread to the other twin, showing that the spread occurred only once.
Single cell transcriptional evolution of myeloid leukemia of Down syndrome
|
Abstract Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), via a conserved sequence of mutations. Here, we examine the relationship between the genetic and transcriptional evolution of ML-DS from natural variation; a rich collection of primary patient samples and foetal tissues with a range of constitutional karyotypes.
By Mi K Trinh, Konstantin Schuschel, Hasan Issa, Rebecca Thomas, Conor Parks, Agnes Oszlanczi, Di Zhou, Lira Mamanova, Elena Prigmore, Angus Hodder, Anna Wenger, Nathaniel Anderson, Holly Whitfield Verified, Taryn D Treger, José Gonçalves-Dias, Karin Straathof, David H. O’Connor, Matthew Young Verified, Laura Jardine, Stuart Adams, Jan-Henning Klusmann, Jack Bartram, Sam Behjati, Toochi Ogbonnah, Emilia R. Robertson
|
Nature
Verified
A non-canonical lymphoblast in refractory childhood T-cell leukaemia - Nature Communications
Abstract Refractory cancers may arise either through the acquisition of resistance mechanisms or represent distinct disease states. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we perform single cell mRNA sequencing of T-ALL from 58 children (84 samples) who did, or did not respond to initial treatment.
Single-cell transcriptomics identifies chondrocyte differentiation dynamics in vivo and in vitro
|
Keywords cartilage single-cell RNA sequencing skeletal development in vitro chondrogenesis Introduction Large-scale single-cell profiling studies have improved our understanding of the cellular composition of multiple organ systems.1 These efforts extend to human development, with profiles of different systems across developmental time providing insight into the origins of a range of diseases.2,3 This knowledge promises to improve the fidelity of in vitro organoid systems, providing both a...
By John Lawrence, Steven Woods, Kenny Roberts, Dinithi Sumanaweera, Petra Balogh, Alexander Predeus, Peng He, Krzysztof Polanski, Elena Prigmore, Elizabeth Tuck, Lira Mamanova, Di Zhou, Simone Webb, Laura Jardine, Xiaoling He, Roger Barker, Muzlifah Haniffa, Adrienne M. Flanagan, Matthew Young Verified, Sam Behjati, Omer A. Bayraktar, Susan J Kimber, Sarah A Teichmann
|
Cell Press
Verified
Lingual hamartoma‐like lipoblastoma: the diagnostic value of routine whole‐genome sequencing
FISH Fluorescent in situ hybridisation NHS National health service WGS whole genome sequencing Paediatric tongue lesions are rare, and diagnostically challenging as a result.1 Histopathology often suffices for diagnosis, but some lesions require molecular assessment for precise characterization.
Primary cartilage transcriptional signatures reflect cell-type-specific molecular pathways underpinning osteoarthritis
Keywords osteoarthritis RNA sequencing chondrocyte populations cell-type-specific expression endochondral ossification gene co-expression networks gene set analysis disease pathways Introduction Osteoarthritis is the most prevalent degenerative joint disorder, affecting over 500 million individuals worldwide.1 It is a complex disease, mainly characterized by loss of cartilage integrity and low-grade inflammation in tissues surrounding the joint.2 Management strategies focus on pain relief and...
Multifocal, multiphenotypic tumours arising from an MTOR mutation acquired in early embryogenesis - Oncogene
Abstract Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing.
Targetable NOTCH1 rearrangements in reninoma - Nature Communications
|
Abstract Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP.
By Henry Lee-Six, Reem Al-Saadi, Matthew Young Verified, Thomas Mitchell, Philip Jones, Sam Behjati, Emilie Abby
|
Nature
Verified
Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia - Nature Medicine
|
Abstract In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells.
By Théo Accogli, Ignacio Criado, Conor Parks, Matthew Young Verified, Robert Lee Wynn, Persis Amrolia, Sam Behjati, Tarryn Porter
|
Nature
Verified
Diagnostic classification of childhood cancer using multiscale transcriptomics - Nature Medicine
Abstract The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes.
Putting bacteria on the cancer map
In a study recently in Nature, Galeano Niño et al. use spatial profiling and single-cell RNA sequencing to delineate the spatial organization of microbiota in cancer. Their findings demonstrate that tumor-associated microbiota coalesce in micro-niches where they may mediate immune and epithelial oncogenic roles.
Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis - Nature Communications
Abstract Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy.
Impact of the COVID-19 pandemic on time to diagnosis and treatment in children with cancer at tertiary care level
http://orcid.org/0000-0001-5768-6777Lionel Dufour1, Ashly Simon2, http://orcid.org/0000-0002-4480-1147Matthew J Murray2,3, Sam Behjati2,4 1 Department of Paediatrics, Barking Havering and Redbridge Hospitals NHS Trust, Romford, UK 2 Cambridge University Hospital NHS Foundation Trust, Cambridge, UK 3 Department of Pathology, University of Cambridge, Cambridge, UK 4 Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK Correspondence to Dr Sam Behjati, Department of Paediatrics, Cambridge...
Clonal diversification and histogenesis of malignant germ cell tumours - Nature Communications
Abstract Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood.
Impact of the COVID-19 pandemic on time to diagnosis and treatment in children with cancer at tertiary care level
child health COVID-19 paediatric emergency medicine The UK NHS responded to the COVID-19 pandemic from early 2020 by focusing all, bar indispensable services, on pandemic management. There are numerous reports of the adverse impact this diversion of resources has had on various health services, including cancer care. The degree to which childhood cancer services have been affected, including diagnostic delay, are less well documented.
Maturation Block in Childhood Cancer
In Focus Sam Behjati, Richard J. Gilbertson and Stefan M. Pfister DOI: 10.1158/2159-8290.CD-20-0926 Published March 2021 This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.
Pitfalls of Applying Mouse Markers to Human Adrenal Medullary Cells
In this letter, we re-analyze human fetal adrenal data generated by Dong et al. to demonstrate the pitfalls of relying on mouse marker genes to annotate human data. We show that unbiased cell label transfer methods imply that neuroblastoma cells resemble sympathoblasts and not chromaffin cells, as Dong et al. had suggested. To read this article in full you will need to make a payment Purchase one-time access Read-It-Now Purchase access to all full-text HTML articles for 6 or 36 hr at a low cost.
Abstract IA28: Tumor uniformity
Abstracts: AACR Special Conference on the Advances in Pediatric Cancer Research; September 17-20, 2019; Montreal, QC, Canada Abstract Intra- and intertumor heterogeneity has emerged as a near-universal feature of human cancer. The definition of heterogeneity has advanced our understanding of various biologic and clinical challenges. At the same time, however, it distracts from unifying features of tumor that may lend themselves as universal targets.
The genetic changes of Wilms tumour
1. Breslow, N., Olshan, A., Beckwith, J. B. & Green, D. M. Epidemiology of Wilms tumor. Med. Pediatr. Oncol. 21, 172–181 (1993). CAS PubMed Article Google Scholar 2. Rivera, M. N. & Haber, D. A. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat. Rev. Cancer 5, 699–712 (2005). CAS PubMed Article Google Scholar 3. Ma, X. et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature 555, 371–376 (2018).
What is next generation sequencing?
There are a number of different NGS platforms using different sequencing technologies, a detailed discussion of which is beyond the scope of this article. However, all NGS platforms perform sequencing of millions of small fragments of DNA in parallel. Bioinformatics analyses are used to piece together these fragments by mapping the individual reads to the human reference genome.
Predisposition to cancer in children and adolescents
Introduction Environmental factors play a minor proven role in childhood cancer. Apart from rare cancers that are caused by viral infections, radiation, oncological, or immunosuppressive therapy, no major environmental causes are proven to be involved in paediatric malignancies. In the past 5 years, the increasing use of next-generation sequencing has led to the discovery of new childhood cancer predisposition syndromes.
Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma
The burden of coding indels and substitutions across the 112 tumours varied from 3 to 316 mutations per tumour (median=38; Supplementary Data 1 and 2). The highest coding mutation burden was observed in PD4901a, a tumour with microsatellite instability. Analysis of 146,573 substitutions in the context of their immediate 5? and 3? bases identified 9 mutational signatures among 37 whole genomes (Supplementary Data 1 and 3). The most prevalent signatures were 5 and 8 (ref. 6).
Genetics: Taking single-cell transcriptomics to the bedside
Refers to Giustacchini, A. et al. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukaemia. Nat. Med. 23, 692–702 (2017) Large-scale transcriptomic studies of human cancers have begun to provide insights into the wealth of biological information encoded in tumour mRNA1. Along with whole-genome DNA sequences, thousands of tumour transcriptomes have been interrogated over the past decade.
Retracing embryological fate
Mammalian development is a beautifully orchestrated process of cell division and differentiation during which the various cell lineages arise that form an organism. The precise nature, origin, and fate of these lineages remain a mystery in humans and in other mammals.
Mutational signatures of ionizing radiation in second malignancies
Informed consent was obtained from all subjects and ethical approval obtained from Cambridgeshire 2 Research Ethics Service (reference 09/H0308/165). Collection and use of patient samples were approved by the appropriate institutional review board of each Institution. DNA was extracted from 12 radiation-associated tumours and subjected to whole-genome sequencing, along with normal tissue derived from the same individuals.
Show More
loading
Actions
Is this you?
As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.Get in touch with Sam
Contact Sam, search articles and posts on X, monitor coverage, and track replies from one place.
Learn more about Muck Rack