Cancer discoveryPub Date : 2025-05-22DOI: 10.1158/2159-8290.cd-25-0375
Yuxuan Wang,Corinne E Joshu,Samuel D Curtis,Christopher Douville,Vernon A Burk,Meng Ru,Maria Popoli,Janine Ptak,Lisa Dobbyn,Natalie Silliman,Josef Coresh,Eric Boerwinkle,Anna Prizment,Chetan Bettegowda,Kenneth W Kinzler,Nickolas Papadopoulos,Elizabeth A Platz,Bert Vogelstein
{"title":"Detection of cancers three years prior to diagnosis using plasma cell-free DNA.","authors":"Yuxuan Wang,Corinne E Joshu,Samuel D Curtis,Christopher Douville,Vernon A Burk,Meng Ru,Maria Popoli,Janine Ptak,Lisa Dobbyn,Natalie Silliman,Josef Coresh,Eric Boerwinkle,Anna Prizment,Chetan Bettegowda,Kenneth W Kinzler,Nickolas Papadopoulos,Elizabeth A Platz,Bert Vogelstein","doi":"10.1158/2159-8290.cd-25-0375","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0375","url":null,"abstract":"To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six participants, the same mutations detected by the MCED test could be identified, but at 8.6 to 79-fold lower mutant allele fractions. These results demonstrate that it is possible to detect circulating tumor DNA more than three years prior to clinical diagnosis, and provide benchmark sensitivities required for this purpose.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"3 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-14DOI: 10.1158/2159-8290.cd-24-1535
Nusrat Khan,Keiko Akagi,Shiming Jiang,Joe Dan Dunn,Bo Jiang,Weihong Xiao,Madison P O'Hara,Li Shen,Qi Wang,Vakul Mohanty,Jing Wang,Sara Goodwin,Jamie L Hutchins,Kevin R Coombes,Jagannadha K Sastry,David E Symer,Maura L Gillison
{"title":"Human papillomavirus integration induces oncogenic host gene fusions in oropharyngeal cancers.","authors":"Nusrat Khan,Keiko Akagi,Shiming Jiang,Joe Dan Dunn,Bo Jiang,Weihong Xiao,Madison P O'Hara,Li Shen,Qi Wang,Vakul Mohanty,Jing Wang,Sara Goodwin,Jamie L Hutchins,Kevin R Coombes,Jagannadha K Sastry,David E Symer,Maura L Gillison","doi":"10.1158/2159-8290.cd-24-1535","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1535","url":null,"abstract":"HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"39 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-12DOI: 10.1158/2159-8290.cd-24-1383
Vindhya Vijay, Negin Karisani, Lei Shi, Yu-Han Hung, Phuong Vu, Prabhat Kattel, Lauren Kenney, Joshua Merritt, Ramzi Adil, Qibiao Wu, Yuanli Zhen, Robert Morris, Johannes Kreuzer, Meena Kathiresan, Xcanda Ixchel. Herrera Lopez, Haley Ellis, Ilaria Gritti, Lilian Lecorgne, Ines Farag, Alexandra Popa, William Shen, Hiroyuki Kato, Qin Xu, Eranga R. Balasooriya, Meng-Ju Wu, Jinkai Wan, Hiroshi Kondo, Saireudee Chaturantabut, Srivatsan Raghavan, Matthew D. Hall, Samarjit Patnaik, Min Shen, Robin K. Kelley, James M. Cleary, Michael S. Lawrence, David E. Root, Krushna C. Patra, Vanessa S. Silveira, Cyril H. Benes, Vikram Deshpande, Dejan Juric, William R. Sellers, Cristina R. Ferrone, Wilhelm Haas, Francisca Vazquez, Gad Getz, Nabeel Bardeesy
{"title":"Generation of a biliary tract cancer cell line atlas identifies molecular subtypes and therapeutic targets","authors":"Vindhya Vijay, Negin Karisani, Lei Shi, Yu-Han Hung, Phuong Vu, Prabhat Kattel, Lauren Kenney, Joshua Merritt, Ramzi Adil, Qibiao Wu, Yuanli Zhen, Robert Morris, Johannes Kreuzer, Meena Kathiresan, Xcanda Ixchel. Herrera Lopez, Haley Ellis, Ilaria Gritti, Lilian Lecorgne, Ines Farag, Alexandra Popa, William Shen, Hiroyuki Kato, Qin Xu, Eranga R. Balasooriya, Meng-Ju Wu, Jinkai Wan, Hiroshi Kondo, Saireudee Chaturantabut, Srivatsan Raghavan, Matthew D. Hall, Samarjit Patnaik, Min Shen, Robin K. Kelley, James M. Cleary, Michael S. Lawrence, David E. Root, Krushna C. Patra, Vanessa S. Silveira, Cyril H. Benes, Vikram Deshpande, Dejan Juric, William R. Sellers, Cristina R. Ferrone, Wilhelm Haas, Francisca Vazquez, Gad Getz, Nabeel Bardeesy","doi":"10.1158/2159-8290.cd-24-1383","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1383","url":null,"abstract":"Biliary tract cancers (BTCs) are aggressive malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we report integrative analysis of 63 BTC cell lines via multi-omics and genome-scale CRISPR screens. We identify widespread EGFR dependency in BTC, alongside dependencies selective to anatomic subtypes. Additionally, we delineate strategies to overcome therapeutic resistance, with combined EGFR inhibition potentiating targeting of KRAS-mutant and FGFR2-fusion-driven models, and SHP2 inhibition effective in the latter context. Clustering RNA/protein expression and dependencies data revealed functional relationships transcending single-gene alterations, with biliary, squamous, or dual biliary/hepatocyte lineage signatures stratifying BTC models. These subtypes exhibit distinct dependency profiles— including cell fate transcription factors GRHL2, TP63, and HNF1B, respectively— and demonstrate prognostic significance in patient samples. Potential subtype-specific targetable vulnerabilities include Integrin-a3 and the detoxification enzyme UXS1. This cell line atlas reveals therapeutic targets in molecularly-defined BTCs, unveils disease subtypes, and provides a resource for therapeutic development.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"27 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-08DOI: 10.1158/2159-8290.cd-24-1678
Meredith S Shiels,Anika T Haque,Amy Berrington de González,M Constanza Camargo,Megan A Clarke,Brittny C Davis Lynn,Eric A Engels,Neal D Freedman,Gretchen L Gierach,Jonathan N Hofmann,Rena R Jones,Erikka Loftfield,Rashmi Sinha,Lindsay M Morton,Stephen J Chanock
{"title":"Trends in Cancer Incidence and Mortality Rates in Early-Onset and Older-Onset Age Groups in the United States, 2010-2019.","authors":"Meredith S Shiels,Anika T Haque,Amy Berrington de González,M Constanza Camargo,Megan A Clarke,Brittny C Davis Lynn,Eric A Engels,Neal D Freedman,Gretchen L Gierach,Jonathan N Hofmann,Rena R Jones,Erikka Loftfield,Rashmi Sinha,Lindsay M Morton,Stephen J Chanock","doi":"10.1158/2159-8290.cd-24-1678","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1678","url":null,"abstract":"In the United States, incidence rates of some cancers have increased in early-onset age groups. For many of these cancers, rates have also increased in older-age groups, suggesting that the impact of changes in risk factor prevalence and/or improvements in detection could affect risk across the age range.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"68 1","pages":"OF1-OF14"},"PeriodicalIF":28.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-08DOI: 10.1158/2159-8290.cd-24-1712
Wenyan Xie, Xin Yu, Qingxin Yang, Nengwen Ke, Ping Wang, Hao Kong, Xiangji Wu, Panpan Ma, Lang Chen, Jie Yang, Xiuqin Feng, Yuan Wang, Hubing Shi, Lu Chen, Yun-Hua Liu, Bi-Sen Ding, Qiang Wei, Hong Jiang
{"title":"An immunomechanical checkpoint PYK2 governs monocyte-to-macrophage differentiation in pancreatic cancer","authors":"Wenyan Xie, Xin Yu, Qingxin Yang, Nengwen Ke, Ping Wang, Hao Kong, Xiangji Wu, Panpan Ma, Lang Chen, Jie Yang, Xiuqin Feng, Yuan Wang, Hubing Shi, Lu Chen, Yun-Hua Liu, Bi-Sen Ding, Qiang Wei, Hong Jiang","doi":"10.1158/2159-8290.cd-24-1712","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1712","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic, stiff tumor microenvironment (TME), where tumor-associated macrophages (TAMs) drive ECM remodeling, progression, and immune evasion. The contribution of mechanical cues to monocyte differentiation into TAMs remains largely unexplored. Here we show that mechanical force is required for monocyte-to-macrophage differentiation. PYK2, as an innovative immunomechanical checkpoint, de facto governs this differentiation process. We demonstrated that PYK2 senses mechanical signals via Piezo1 and integrins, triggering F-actin polymerization and translocating to the nucleus to regulate mechanotransduction and differentiation genes (e.g., ACTR3, RELA). Targeted deletion of PYK2 impairs the differentiation and polarization of monocyte-derived macrophages, reshapes the PDAC microenvironment, and enhances the efficacy of anti-PD-1 immunotherapy. These findings underscore the critical role of mechanical cues in monocyte differentiation and suggest that targeting PYK2 is a promising strategy to modulate TAM function and improve immunotherapy outcomes in patients with PDAC.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"8 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-07DOI: 10.1158/2159-8290.CD-24-1532
Wei Lv, Yuchen Zeng, Conghui Li, Yuan Liang, Huiying Tao, Yanfen Zhu, Xiaolong Sui, Yue Li, Shiqi Jiang, Qingqing Gao, Elias Rodriguez-Fos, Gino Prasad, Yuanmei Wang, Run Zhou, Zhe Xu, Xiaoguang Pan, Linlin Chen, Xi Xiang, Huajing Teng, Chaoyang Sun, Tianyu Qin, Wei Dong, Yongwei Li, Xun Lan, Xuesong Li, Lin Lin, Lars Bolund, Huanming Yang, Roel G W Verhaak, Bishoy M Faltas, Jacob B Hansen, Sihan Wu, Paul S Mischel, Anton G Henssen, Vineet Bafna, Jens Luebeck, Birgitte Regenberg, Yonglun Luo, Chunhua Lin, Peng Han
{"title":"Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment.","authors":"Wei Lv, Yuchen Zeng, Conghui Li, Yuan Liang, Huiying Tao, Yanfen Zhu, Xiaolong Sui, Yue Li, Shiqi Jiang, Qingqing Gao, Elias Rodriguez-Fos, Gino Prasad, Yuanmei Wang, Run Zhou, Zhe Xu, Xiaoguang Pan, Linlin Chen, Xi Xiang, Huajing Teng, Chaoyang Sun, Tianyu Qin, Wei Dong, Yongwei Li, Xun Lan, Xuesong Li, Lin Lin, Lars Bolund, Huanming Yang, Roel G W Verhaak, Bishoy M Faltas, Jacob B Hansen, Sihan Wu, Paul S Mischel, Anton G Henssen, Vineet Bafna, Jens Luebeck, Birgitte Regenberg, Yonglun Luo, Chunhua Lin, Peng Han","doi":"10.1158/2159-8290.CD-24-1532","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-1532","url":null,"abstract":"<p><strong>Significance: </strong>Our comprehensive analysis of ecDNA in urothelial carcinoma reveals its crucial role in driving the evolution and heterogeneity of multifocal cancer, as well as its early involvement in tumorigenesis. Moreover, this study sheds light on immune evasion mechanisms associated with ecDNA and offers valuable insights for developing targeted therapeutic strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1-OF22"},"PeriodicalIF":29.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling.","authors":"Jayadev Mavuluri, Yogesh Dhungana, Lindsay L Jones, Sheetal Bhatara, Hao Shi, Xu Yang, Song-Eun Lim, Noemi Reyes, Hongbo Chi, Jiyang Yu, Terrence L Geiger","doi":"10.1158/2159-8290.CD-24-0841","DOIUrl":"10.1158/2159-8290.CD-24-0841","url":null,"abstract":"<p><strong>Significance: </strong>The study identifies GPR65 as an important determinant of B-cell acute lymphoblastic leukemia response to CAR T-cell therapy. Notably, GPR65 absence signals CAR T resistance. By emphasizing the therapeutic potential of targeting VEGFA or host macrophages, our study identifies routes to optimize CAR T-cell therapy outcomes in hematologic malignancies via tumor microenvironment manipulation.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1018-1036"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.cd-25-0099
Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,
{"title":"MANIFEST: Multiomic Platform for Cancer Immunotherapy.","authors":"Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,","doi":"10.1158/2159-8290.cd-25-0099","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0099","url":null,"abstract":"Immunotherapy has revolutionized survival outcomes for many patients diagnosed with cancer. However, biomarkers that can reliably distinguish treatment responders from nonresponders, predict potential life-threatening and life-changing drug-induced toxicities, or rationalize treatment choices are still lacking. In response to this unmet clinical need, we introduce Multiomic ANalysis of Immunotherapy Features Evidencing Success and Toxicity, a tumor type-agnostic platform to provide deep profiling of patients receiving immunotherapy that will enable integrative identification of biomarkers and discovery of novel targets using artificial intelligence and machine learning.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"118 1","pages":"878-883"},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.CD-23-0882
Takafumi N Yamaguchi, Kathleen E Houlahan, Helen Zhu, Natalie Kurganovs, Julie Livingstone, Natalie S Fox, Jiapei Yuan, Jocelyn Sietsma Penington, Chol-Hee Jung, Tommer Schwarz, Weerachai Jaratlerdsiri, Job van Riet, Peter Georgeson, Stefano Mangiola, Kodi Taraszka, Robert Lesurf, Jue Jiang, Ken Chow, Lawrence E Heisler, Yu-Jia Shiah, Susmita G Ramanand, Michael J Clarkson, Anne Nguyen, Shadrielle Melijah G Espiritu, Ryan Stuchbery, Richard Jovelin, Vincent Huang, Connor Bell, Edward O'Connor, Patrick J McCoy, Christopher M Lalansingh, Marek Cmero, Adriana Salcedo, Eva K F Chan, Lydia Y Liu, Phillip D Stricker, Vinayak Bhandari, Riana M S Bornman, Dorota H S Sendorek, Andrew Lonie, Stephenie D Prokopec, Michael Fraser, Justin S Peters, Adrien Foucal, Shingai B A Mutambirwa, Lachlan Mcintosh, Michèle Orain, Matthew Wakefield, Valérie Picard, Daniel J Park, Hélène Hovington, Michael Kerger, Alain Bergeron, Veronica Sabelnykova, Ji-Heui Seo, Mark M Pomerantz, Noah Zaitlen, Sebastian M Waszak, Alexander Gusev, Louis Lacombe, Yves Fradet, Andrew Ryan, Amar U Kishan, Martijn P Lolkema, Joachim Weischenfeldt, Bernard Têtu, Anthony J Costello, Vanessa M Hayes, Rayjean J Hung, Housheng H He, John D McPherson, Bogdan Pasaniuc, Theodorus van der Kwast, Anthony T Papenfuss, Matthew L Freedman, Bernard J Pope, Robert G Bristow, Ram S Mani, Niall M Corcoran, Jüri Reimand, Christopher M Hovens, Paul C Boutros
{"title":"The Germline and Somatic Origins of Prostate Cancer Heterogeneity.","authors":"Takafumi N Yamaguchi, Kathleen E Houlahan, Helen Zhu, Natalie Kurganovs, Julie Livingstone, Natalie S Fox, Jiapei Yuan, Jocelyn Sietsma Penington, Chol-Hee Jung, Tommer Schwarz, Weerachai Jaratlerdsiri, Job van Riet, Peter Georgeson, Stefano Mangiola, Kodi Taraszka, Robert Lesurf, Jue Jiang, Ken Chow, Lawrence E Heisler, Yu-Jia Shiah, Susmita G Ramanand, Michael J Clarkson, Anne Nguyen, Shadrielle Melijah G Espiritu, Ryan Stuchbery, Richard Jovelin, Vincent Huang, Connor Bell, Edward O'Connor, Patrick J McCoy, Christopher M Lalansingh, Marek Cmero, Adriana Salcedo, Eva K F Chan, Lydia Y Liu, Phillip D Stricker, Vinayak Bhandari, Riana M S Bornman, Dorota H S Sendorek, Andrew Lonie, Stephenie D Prokopec, Michael Fraser, Justin S Peters, Adrien Foucal, Shingai B A Mutambirwa, Lachlan Mcintosh, Michèle Orain, Matthew Wakefield, Valérie Picard, Daniel J Park, Hélène Hovington, Michael Kerger, Alain Bergeron, Veronica Sabelnykova, Ji-Heui Seo, Mark M Pomerantz, Noah Zaitlen, Sebastian M Waszak, Alexander Gusev, Louis Lacombe, Yves Fradet, Andrew Ryan, Amar U Kishan, Martijn P Lolkema, Joachim Weischenfeldt, Bernard Têtu, Anthony J Costello, Vanessa M Hayes, Rayjean J Hung, Housheng H He, John D McPherson, Bogdan Pasaniuc, Theodorus van der Kwast, Anthony T Papenfuss, Matthew L Freedman, Bernard J Pope, Robert G Bristow, Ram S Mani, Niall M Corcoran, Jüri Reimand, Christopher M Hovens, Paul C Boutros","doi":"10.1158/2159-8290.CD-23-0882","DOIUrl":"10.1158/2159-8290.CD-23-0882","url":null,"abstract":"<p><strong>Significance: </strong>This study uncovered 223 recurrently mutated driver regions using the largest cohort of prostate tumors to date. It reveals associations between germline SNPs, somatic drivers, and tumor aggression, offering significant insights into how prostate tumor evolution is shaped by germline factors and the timing of somatic mutations.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"988-1017"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.cd-25-0209
Ken Furudate, Koichi Takahashi
{"title":"Prenatal Chemotherapy and Its Impact on the Genome of Fetal Hematopoiesis","authors":"Ken Furudate, Koichi Takahashi","doi":"10.1158/2159-8290.cd-25-0209","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0209","url":null,"abstract":"Summary: The genotoxic impact of cancer chemotherapy administered during pregnancy on neonatal hematopoietic cells remains largely unknown. In this study, Struys and colleagues demonstrate that prenatal chemotherapy exposure leads to an increased somatic mutational burden in neonatal hematopoietic stem and progenitor cells, characterized by distinct mutational signatures, revealing a previously unrecognized consequence of in utero chemotherapy on fetal hematopoiesis and underscoring the need for further research to assess its long-term implications and potential risks. See related article by Struys et al., p. 903","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"34 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
