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1دورية أكاديمية
المؤلفون: Lindsay M. Morton, Olivia W. Lee, Danielle M. Karyadi, Tetiana I. Bogdanova, Chip Stewart, Stephen W. Hartley, Charles E. Breeze, Sara J. Schonfeld, Elizabeth K. Cahoon, Vladimir Drozdovitch, Sergii Masiuk, Mykola Chepurny, Liudmyla Yu Zurnadzhy, Jieqiong Dai, Marko Krznaric, Meredith Yeager, Amy Hutchinson, Belynda D. Hicks, Casey L. Dagnall, Mia K. Steinberg, Kristine Jones, Komal Jain, Ben Jordan, Mitchell J. Machiela, Eric T. Dawson, Vibha Vij, Julie M. Gastier-Foster, Jay Bowen, Kiyohiko Mabuchi, Maureen Hatch, Amy Berrington de Gonzalez, Gad Getz, Mykola D. Tronko, Gerry A. Thomas, Stephen J. Chanock
المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
مصطلحات موضوعية: Science
الوصف: Abstract Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
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2دورية أكاديمية
المؤلفون: Chunyang Bao, Richard W. Tourdot, Gregory J. Brunette, Chip Stewart, Lili Sun, Hideo Baba, Masayuki Watanabe, Agoston T. Agoston, Kunal Jajoo, Jon M. Davison, Katie S. Nason, Gad Getz, Kenneth K. Wang, Yu Imamura, Robert Odze, Adam J. Bass, Matthew D. Stachler, Cheng-Zhong Zhang
المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-22 (2023)
مصطلحات موضوعية: Science
الوصف: Abstract The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
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3دورية أكاديمية
المؤلفون: Andreas Varkaris, Ferran Fece de la Cruz, Elizabeth E. Martin, Bryanna L. Norden, Nicholas Chevalier, Allison M. Kehlmann, Ignaty Leshchiner, Haley Barnes, Sara Ehnstrom, Anastasia-Maria Stavridi, Xin Yuan, Janice S. Kim, Haley Ellis, Alkistis Papatheodoridi, Hakan Gunaydin, Brian P. Danysh, Laxmi Parida, Ioannis Sanidas, Yongli Ji, Kayao Lau, Gerburg M. Wulf, Aditya Bardia, Laura M. Spring, Steven J. Isakoff, Jochen K. Lennerz, Kathryn Del Vecchio, Levi Pierce, Ermira Pazolli, Gad Getz, Ryan B. Corcoran, Dejan Juric
مصطلحات موضوعية: Cancer, Methods and Technology, Liquid Biopsy
الوصف: Supplementary Figure S1: PI3K pathway activity in selected cases with acquired PTEN alteration. Supplementary Figure S2. Validation of AKT constructs expression in T47D cells. Supplementary Figure S3. AKT activating mutations confer resistance to PI3Ka inhibitors. Supplementary Figure S4: Free energy calculations predict resistance to orthosteric PI3K inhibitors due to specific double PIK3CA mutants. Supplementary Figure S5: Free energy perturbation predicts reduced binding of orthosteric PI3K inhibitors to double mutants. Supplementary Figure S6. Expression of PIK3CA mutations in T47D cells. Supplementary Figure S7. MCF7 cells expressing W780R or Q859H double mutants show differential response to PIK3CA orthosteric inhibitors. Supplementary Figure S8: Chemical structure of RLY-2608. Supplementary Figure S9: Surface plasmon resonance (SPR) binding assay. Supplementary Figure S10. Alpelisib shows reduced potency of downstream signaling inhibition in the presence of W780R or Q859H/K. Supplementary Figure S11. T47D cells expressing I817F or E726K double mutants do not show a differential response to inavolisib (A) or RLY-2608 (B).
الإتاحة: https://doi.org/10.1158/2159-8290.25183861.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Figures_S1_to_S11_from_Allosteric_PI3K_Inhibition_Overcomes_On-target_Resistance_to_Orthosteric_Inhibitors_Mediated_by_Secondary_i_PIK3CA_i_Mutations/25183861Test -
4دورية أكاديمية
المؤلفون: Andreas Varkaris, Ferran Fece de la Cruz, Elizabeth E. Martin, Bryanna L. Norden, Nicholas Chevalier, Allison M. Kehlmann, Ignaty Leshchiner, Haley Barnes, Sara Ehnstrom, Anastasia-Maria Stavridi, Xin Yuan, Janice S. Kim, Haley Ellis, Alkistis Papatheodoridi, Hakan Gunaydin, Brian P. Danysh, Laxmi Parida, Ioannis Sanidas, Yongli Ji, Kayao Lau, Gerburg M. Wulf, Aditya Bardia, Laura M. Spring, Steven J. Isakoff, Jochen K. Lennerz, Kathryn Del Vecchio, Levi Pierce, Ermira Pazolli, Gad Getz, Ryan B. Corcoran, Dejan Juric
مصطلحات موضوعية: Cancer, Methods and Technology, Liquid Biopsy
الوصف: Table S1: Eligibility Criteria. Table S2: Genomic alterations within the PIK3CA pathway and other documented alterations for this study. Table S3: VAF of EOT alterations. Table S4: Comparison of Acquired PIK3CA mutations based on baseline activating mutation. Table S5: Comparison of Acquired PIK3CA mutations based on number of baseline activating PIK3CA mutations.
الإتاحة: https://doi.org/10.1158/2159-8290.25183858.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Tables_S1_to_S5_from_Allosteric_PI3K_Inhibition_Overcomes_On-target_Resistance_to_Orthosteric_Inhibitors_Mediated_by_Secondary_i_PIK3CA_i_Mutations/25183858Test -
5دورية أكاديمية
المؤلفون: Anirban Das, Nicholas R. Fernandez, Adrian Levine, Vanessa Bianchi, Lucie K. Stengs, Jiil Chung, Logine Negm, Jose Rafael Dimayacyac, Yuan Chang, Liana Nobre, Ayse B. Ercan, Santiago Sanchez-Ramirez, Sumedha Sudhaman, Melissa Edwards, Valerie Larouche, David Samuel, An Van Damme, David Gass, David S. Ziegler, Stefan S. Bielack, Carl Koschmann, Shayna Zelcer, Michal Yalon-Oren, Gadi Abede Campino, Tomasz Sarosiek, Kim E. Nichols, Rebecca Loret De Mola, Kevin Bielamowicz, Magnus Sabel, Charlotta A. Frojd, Matthew D. Wood, Jason M. Glover, Yi-Yen Lee, Magimairajan Vanan, Jenny K. Adamski, Sebastien Perreault, Omar Chamdine, Magnus Aasved Hjort, Michal Zapotocky, Fernando Carceller, Erin Wright, Ivana Fedorakova, Alexander Lossos, Ryuma Tanaka, Michael Osborn, Deborah T. Blumenthal, Melyssa Aronson, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Malkin, Adam Shlien, Anita Villani, Peter B. Dirks, Trevor J. Pugh, Gad Getz, Yosef E. Maruvka, Derek S. Tsang, Birgit Ertl-Wagner, Cynthia Hawkins, Eric Bouffet, Daniel A. Morgenstern, Uri Tabori
مصطلحات موضوعية: Cancer, Tumor Biology, Cancer Detection and Diagnosis, Therapeutic Research and Development, Immuno-oncology, Clinical Research and Trials, Biomarkers, Clinical-stage Research, CNS Cancers, Gliomas, Glioblastomas, Immunotherapy, Checkpoint blockade, Pediatric Cancers, Translational Research, Tumor Evolution, Tumor Microenvironment
الوصف: Supplementary Figures S1 to S5, with each figure followed by its corresponding legend in the next page
الإتاحة: https://doi.org/10.1158/2159-8290.25183895.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Figures_S1-S5_from_Combined_Immunotherapy_Improves_Outcome_for_Replication-Repair-Deficient_RRD_High-Grade_Glioma_Failing_Anti_PD-1_Monotherapy_A_Report_from_the_International_RRD_Consortium/25183895Test -
6دورية أكاديمية
المؤلفون: Anirban Das, Nicholas R. Fernandez, Adrian Levine, Vanessa Bianchi, Lucie K. Stengs, Jiil Chung, Logine Negm, Jose Rafael Dimayacyac, Yuan Chang, Liana Nobre, Ayse B. Ercan, Santiago Sanchez-Ramirez, Sumedha Sudhaman, Melissa Edwards, Valerie Larouche, David Samuel, An Van Damme, David Gass, David S. Ziegler, Stefan S. Bielack, Carl Koschmann, Shayna Zelcer, Michal Yalon-Oren, Gadi Abede Campino, Tomasz Sarosiek, Kim E. Nichols, Rebecca Loret De Mola, Kevin Bielamowicz, Magnus Sabel, Charlotta A. Frojd, Matthew D. Wood, Jason M. Glover, Yi-Yen Lee, Magimairajan Vanan, Jenny K. Adamski, Sebastien Perreault, Omar Chamdine, Magnus Aasved Hjort, Michal Zapotocky, Fernando Carceller, Erin Wright, Ivana Fedorakova, Alexander Lossos, Ryuma Tanaka, Michael Osborn, Deborah T. Blumenthal, Melyssa Aronson, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Malkin, Adam Shlien, Anita Villani, Peter B. Dirks, Trevor J. Pugh, Gad Getz, Yosef E. Maruvka, Derek S. Tsang, Birgit Ertl-Wagner, Cynthia Hawkins, Eric Bouffet, Daniel A. Morgenstern, Uri Tabori
مصطلحات موضوعية: Cancer, Tumor Biology, Cancer Detection and Diagnosis, Therapeutic Research and Development, Immuno-oncology, Clinical Research and Trials, Biomarkers, Clinical-stage Research, CNS Cancers, Gliomas, Glioblastomas, Immunotherapy, Checkpoint blockade, Pediatric Cancers, Translational Research, Tumor Evolution, Tumor Microenvironment
الوصف: Demographics and details of treatment in patients who continued ICI progression (n=38)
الإتاحة: https://doi.org/10.1158/2159-8290.25183886.v1Test
https://figshare.com/articles/journal_contribution/Table_S2_from_Combined_Immunotherapy_Improves_Outcome_for_Replication-Repair-Deficient_RRD_High-Grade_Glioma_Failing_Anti_PD-1_Monotherapy_A_Report_from_the_International_RRD_Consortium/25183886Test -
7دورية أكاديمية
المؤلفون: Rebecca Boiarsky, Nicholas J. Haradhvala, Jean-Baptiste Alberge, Romanos Sklavenitis-Pistofidis, Tarek H. Mouhieddine, Oksana Zavidij, Ming-Chieh Shih, Danielle Firer, Mendy Miller, Habib El-Khoury, Shankara K. Anand, François Aguet, David Sontag, Irene M. Ghobrial, Gad Getz
المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-15 (2022)
مصطلحات موضوعية: Science
الوصف: Development of multiple myeloma is preceded by precursor conditions. Here, the authors use single cell RNA-sequencing of plasma cells from patients across disease stages to identify genomic signatures present even at the earliest stages of disease.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
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8دورية أكاديمية
المؤلفون: Mark Bustoros, Shankara Anand, Romanos Sklavenitis-Pistofidis, Robert Redd, Eileen M. Boyle, Benny Zhitomirsky, Andrew J. Dunford, Yu-Tzu Tai, Selina J. Chavda, Cody Boehner, Carl Jannes Neuse, Mahshid Rahmat, Ankit Dutta, Tineke Casneuf, Raluca Verona, Efstathis Kastritis, Lorenzo Trippa, Chip Stewart, Brian A. Walker, Faith E. Davies, Meletios-Athanasios Dimopoulos, P. Leif Bergsagel, Kwee Yong, Gareth J. Morgan, François Aguet, Gad Getz, Irene M. Ghobrial
المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-10 (2022)
مصطلحات موضوعية: Science
الوصف: Existing clinical models cannot fully capture smoldering multiple myeloma (SMM) heterogeneity. Here, integration of 42 genetic alterations from 214 SMM patients using an unsupervised binary matrix factorization clustering approach results in the identification of 6 distinct molecular and clinical subtypes.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
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9مورد إلكتروني
المؤلفون: Mark Holton, Monica Arniella, Arvind Ravi, Gad Getz
مصطلحات موضوعية: lung cancer, immunotherapy
الوصف: Supplemental code and data accompanying the manuscript, "Genomic and Transcriptomic Analysis of Checkpoint Blockade Response in Advanced Non-Small Cell Lung Cancer." ...
العلاقة: https://dx.doi.org/10.5281/zenodo.7625517Test; https://dx.doi.org/10.5281/zenodo.7849582Test; https://dx.doi.org/10.5281/zenodo.11179623Test
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10دورية أكاديمية
المؤلفون: Ankit K. Dutta, Jean-Baptiste Alberge, Elizabeth D. Lightbody, Cody J. Boehner, Andrew Dunford, Romanos Sklavenitis-Pistofidis, Tarek H. Mouhieddine, Annie N. Cowan, Nang Kham Su, Erica M. Horowitz, Hadley Barr, Laura Hevenor, Jenna B. Beckwith, Jacqueline Perry, Amanda Cao, Ziao Lin, Frank K. Kuhr, Richard G. Del Mastro, Omar Nadeem, Patricia T. Greipp, Chip Stewart, Daniel Auclair, Gad Getz, Irene M. Ghobrial
مصطلحات موضوعية: Cancer
الوصف: Supplementary data contains additional Materials and Methods used to generate results presented only in the supplementary figures and tables, as well as more detailed bioinformatics methods. Figure S1 shows correlation between clinical measures of disease pathology, survival, and circulating tumor cells enumeration. Figure S2 shows characteristics of isolated circulating tumor cells from peripheral blood of precursor disease patients. Figure S3 shows cohort-level genomic characterization of tumor in MM precursor stages with CTCs. Figure S4 shows longitudinal and tissue-matched genomic characterization of driver mutations. Figure S5 shows comparison of mutational processes between BMPCs and CTCs assigned to most likely PCAWG composite reference signature. Table S1 shows clinical characteristics and sampling of participants in this study. Table S2 shows whole-genome sequencing coverage and library metrics. Table S3 shows clinical BM FISH results and cells recovered for cohort with matched samples. Table S4 shows comparison of BCR sequence between BMPCs and CTCs. Table S5 shows clinical BM FISH results of peripheral blood only cohort and CTCs recovered. Table S6 shows enumeration of single nucleotide variants and short insertions and deletions discovered from WGS of CTCs. Table S7 shows enumeration of structural variants reconstructed from WGS of CTCs.
الإتاحة: https://doi.org/10.1158/2159-8290.24525047.v1Test
https://figshare.com/articles/journal_contribution/Supplementary_Figures_and_Tables_from_MinimuMM-seq_Genome_Sequencing_of_Circulating_Tumor_Cells_for_Minimally_Invasive_Molecular_Characterization_of_Multiple_Myeloma_Pathology/24525047Test
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