المؤلفون: Simon Mantha, Michael F. Berger, Ryan Ptashkin, Lior Z. Braunstein, Yangyu Zhou, Ederlinda Paraiso, Barbara Spitzer, Kamal Menghrajani, Ross L. Levine, Mariko Yabe, Ryma Benayed, David B. Solit, Daniel Kelly, John Philip, Juan S. Medina Martinez, Sean M. Devlin, Sebastià Franch-Expósito, Luis A. Diaz, Nicole M. Caltabellotta, Elsa Bernard, Max Levine, Teng Gao, Elli Papaemmanuil, Virginia M. Klimek, Minal Patel, Ahmet Zehir, Yanming Zhang, Kelly L. Bolton, Maria Sirenko, Juan E. Arango Ossa, Christopher J. Fong

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021)
Nature Communications

مصطلحات موضوعية: 0301 basic medicine, Adult, Science, Predictive medicine, General Physics and Astronomy, Gene mutation, Biology, Predictive markers, Somatic evolution in cancer, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, Article, Evolutionary genetics, Clonal Evolution, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neoplasms, Genotype, medicine, Cancer genomics, Humans, Cumulative incidence, Risk factor, Selection, Genetic, Aged, Aged, 80 and over, Chromosome Aberrations, Multidisciplinary, Mosaicism, Cancer, Diagnostic markers, General Chemistry, Middle Aged, medicine.disease, Haematopoiesis, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Mutation, Cancer research, Clonal Hematopoiesis

الوصف: Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P
Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32064e47fe72a93319ba11e24a4dc092Test
https://doaj.org/article/86f1527efcbe4a8c928f5380279e4756Test

المؤلفون: Peng Yang, Hsian-Rong Tseng, Yingying Yang, Steven-Huy B. Han, Juvelyn Palomique, Dongping Qi, Pin-Jung Chen, Nicolas Nissen, Edwin M. Posadas, Matthew Smalley, Pai-Chi Teng, Saeed Sadeghi, Jing Wang, Jasmine J. Wang, Shih-Jie Chou, Rueihung Kao, Sungyong You, Na Sun, David Elashoff, Huiying Li, Yi-Te Lee, Vatche G. Agopian, Xinyue Zhang, Richard S. Finn, Anthony P. Heaney, Ryan Y. Zhang, Sammy Saab, Lirong Bao, Hsiao-hua Yu, Yazhen Zhu, Daniela Markovic, Ju Dong Yang, Minhyung Kim, Renjun Pei, Ronald W. Busuttil

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020)
Nature communications, vol 11, iss 1
Nature Communications

مصطلحات موضوعية: Liver Cirrhosis, Male, 0301 basic medicine, Hepatocellular carcinoma, Microfluidics, Messenger, General Physics and Astronomy, Computational Chemistry, 0302 clinical medicine, Lab-On-A-Chip Devices, Diagnosis, Digital polymerase chain reaction, lcsh:Science, Early Detection of Cancer, Cancer, Tumor, Multidisciplinary, Plasma samples, Reverse Transcriptase Polymerase Chain Reaction, Chemistry, Liver Disease, Liver Neoplasms, Hep G2 Cells, Extracellular vesicle, Microfluidic Analytical Techniques, Middle Aged, 030220 oncology & carcinogenesis, Early hcc, Disease Progression, Female, Liver Cancer, Carcinoma, Hepatocellular, Science, Early detection, Extracellular vesicles, Article, General Biochemistry, Genetics and Molecular Biology, Diagnosis, Differential, Cancer screening, Extracellular Vesicles, 03 medical and health sciences, Rare Diseases, Biomarkers, Tumor, Carcinoma, medicine, Humans, Computer Simulation, RNA, Messenger, Dimethylpolysiloxanes, neoplasms, Neoplasm Staging, Aged, Nanowires, Prevention, Liquid Biopsy, Diagnostic markers, Hepatocellular, General Chemistry, medicine.disease, digestive system diseases, Nanostructures, 030104 developmental biology, ROC Curve, Case-Control Studies, Differential, Cancer research, RNA, Click Chemistry, lcsh:Q, Digestive Diseases, Biomarkers

الوصف: We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).
Extracellular vesicles (EVs) are present in circulation at relatively early stages of disease, providing potential opportunities for early cancer diagnosis. Here, the authors report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific EV purification system for early detection of HCC by performing digital scoring on the purified EVs.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51caeb4f2846ec961920a138ab832b13Test
http://link.springer.com/article/10.1038/s41467-020-18311-0Test

المؤلفون: Jun Cheng, Jie Zhang, Dong Ni, Liang Cheng, Kun Huang, Wei Shao, Zhi Han, Qianjin Feng, Michael Cheng, Rohit Mehra

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-9 (2020)
Nature Communications

مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Science, H&E stain, General Physics and Astronomy, TFE3, urologic and male genital diseases, General Biochemistry, Genetics and Molecular Biology, Article, Translocation, Genetic, Xp11 2 translocation, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Image processing, Renal cell carcinoma, medicine, Image Processing, Computer-Assisted, Humans, lcsh:Science, Pathological, neoplasms, Carcinoma, Renal Cell, In Situ Hybridization, Fluorescence, Multidisciplinary, business.industry, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cancer, Computational Biology, Diagnostic markers, General Chemistry, medicine.disease, female genital diseases and pregnancy complications, Kidney Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Histopathology, Female, lcsh:Q, business, Clear cell

الوصف: TFE3 Xp11.2 translocation renal cell carcinoma (TFE3-RCC) generally progresses more aggressively compared with other RCC subtypes, but it is challenging to diagnose TFE3-RCC by traditional visual inspection of pathological images. In this study, we collect hematoxylin and eosin- stained histopathology whole-slide images of 74 TFE3-RCC cases (the largest cohort to date) and 74 clear cell RCC cases (ccRCC, the most common RCC subtype) with matched gender and tumor grade. An automatic computational pipeline is implemented to extract image features. Comparative study identifies 52 image features with significant differences between TFE3-RCC and ccRCC. Machine learning models are built to distinguish TFE3-RCC from ccRCC. Tests of the classification models on an external validation set reveal high accuracy with areas under ROC curve ranging from 0.842 to 0.894. Our results suggest that automatically derived image features can capture subtle morphological differences between TFE3-RCC and ccRCC and contribute to a potential guideline for TFE3-RCC diagnosis.
Translocation renal cell carcinoma is an aggressive form of renal cancer that is often misdiagnosed to other subtypes. Here the authors demonstrated that by using machine learning and H&E stained whole-slide images, an accurate diagnose of this particular type of renal cancer can be achieved.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51b0869c9dbbd7593e0b57948c73b48eTest
http://link.springer.com/article/10.1038/s41467-020-15671-5Test

المؤلفون: Christian Fougner, Therese Sørlie, Helga Bergholtz, Jens Henrik Norum

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020)
Nature Communications

مصطلحات موضوعية: 0301 basic medicine, Genome instability, Stromal cell, endocrine system diseases, Classification and taxonomy, Science, General Physics and Astronomy, Breast Neoplasms, Biology, urologic and male genital diseases, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, Immune system, Breast cancer, 0302 clinical medicine, Gene expression, Biomarkers, Tumor, medicine, Humans, lcsh:Science, skin and connective tissue diseases, Cancer, Regulation of gene expression, Multidisciplinary, Gene Expression Profiling, Diagnostic markers, General Chemistry, Claudin-Low, medicine.disease, Phenotype, digestive system diseases, Gene Expression Regulation, Neoplastic, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, Claudins, Cancer research, Female, lcsh:Q, tissues

الوصف: The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors are distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflect characteristics of their intrinsic subtype. Finally, we explore an alternative method for identifying claudin-low tumors and thereby uncover potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.
In breast cancer, the claudin-low breast cancer subtype is remarkably diverse. Here, the authors propose that claudin-low is not a classical intrinsic breast cancer subtype, but rather a complex additional phenotype that can occur across intrinsic subtypes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::90696509b3868e4bc726a927f11d5d96Test
https://doaj.org/article/cda6d23debbe4bd5b9bd7b754c0eb7c2Test

المؤلفون: Sieverling, Lina, Hong, Chen, Koser, Sandra D., Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M., Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J., Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D.L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Imielinski, Marcin, Jones, David T.W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Sidiropoulos, Nikos, Weischenfeldt, Joachim

المساهمون: Sieverling, Lina [0000-0002-0595-4976], Hong, Chen [0000-0003-1244-3506], Hutter, Barbara [0000-0002-9034-0329], Braun, Delia M [0000-0002-6059-7588], Cortés-Ciriano, Isidro [0000-0002-2036-494X], Xi, Ruibin [0000-0001-7545-7361], Park, Peter J [0000-0001-9378-960X], Schlesner, Matthias [0000-0002-5896-4086], Rippe, Karsten [0000-0001-9951-9395], Apollo - University of Cambridge Repository, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division

المصدر: Nature Communications
Nature communications, vol 11, iss 1
Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020)
Nature Communications, 11
Nature Communications, 11, 1
Sieverling, L, Hong, C, Koser, S D, Ginsbach, P, Kleinheinz, K, Hutter, B, Braun, D M, Cortés-Ciriano, I, Xi, R, Kabbe, R, Park, P J, Eils, R, Schlesner, M, Akdemir, K C, Alvarez, E G, Baez-Ortega, A, Beroukhim, R, Boutros, P C, Bowtell, D D L, Brors, B, Burns, K H, Campbell, P J, Chan, K, Chen, K, Cortés-Ciriano, I, Dueso-Barroso, A, Dunford, A J, Edwards, P A, Estivill, X, Etemadmoghadam, D, Feuerbach, L, Fink, J L, Frenkel-Morgenstern, M, Garsed, D W, Gerstein, M, Gordenin, D A, Haan, D, Haber, J E, Hess, J M, Hutter, B, Imielinski, M, Jones, D T W, Ju, Y S, Kazanov, M D, Klimczak, L J, Koh, Y, Korbel, J O, Kumar, K, Sidiropoulos, N, Weischenfeldt, J, PCAWG Structural Variation Working Group & PCAWG Consortium 2020, ' Genomic footprints of activated telomere maintenance mechanisms in cancer ', Nature Communications, vol. 11, no. 1, 733 . https://doi.org/10.1038/s41467-019-13824-9Test

مصطلحات موضوعية: 0301 basic medicine, Telomerase, Somatic cell, Medizin, General Physics and Astronomy, medicine.disease_cause, Genome, Repetitive Sequences, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Cancer genomics, lcsh:Science, Càncer, Cancer genetics, Cancer, Telomere-binding protein, Genetics, Mutation, 0303 health sciences, Multidisciplinary, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Telòmer, DNA damage and repair, 3rd-DAS, Telomere, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 030220 oncology & carcinogenesis, RNA, Long Noncoding, Long Noncoding, Co-Repressor Proteins, Human, Biotechnology, X-linked Nuclear Protein, Science, Genomics, QH426 Genetics, Biology, General Biochemistry, Genetics and Molecular Biology, Article, RC0254, 03 medical and health sciences, Death-associated protein 6, Rare Diseases, SDG 3 - Good Health and Well-being, Matters Arising, medicine, Humans, ddc:610, QH426, ATRX, 030304 developmental biology, Repetitive Sequences, Nucleic Acid, Tumors, Whole genome sequencing, Nucleic Acid, Whole Genome Sequencing, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Genome, Human, Breakpoint, Human Genome, PCAWG-Structural Variation Working Group, PCAWG Consortium, Diagnostic markers, General Chemistry, medicine.disease, Computational biology and bioinformatics, Genòmica, 030104 developmental biology, chemistry, Case-Control Studies, RNA, lcsh:Q, DNA, Molecular Chaperones

الوصف: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

وصف الملف: application/pdf; application/zip; text/xml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::19d7209aaca5cdce5449b93eccc83971Test
http://europepmc.org/articles/PMC7002710Test