Article
Oncology
Simona Corso, Filippo Pietrantonio, Maria Apicella, Cristina Migliore, Daniela Conticelli, Annalisa Petrelli, Laura D'Errico, Stefania Durando, Daniel Moya-Rull, Sara E. Bellomo, Stefano Ughetto, Maurizio Degiuli, Rossella Reddavid, Uberto Fumagalli, Stefano De Pascale, Giovanni Sgroi, Emanuele Rausa, Gian Luca Baiocchi, Sarah Molfino, Giovanni De Manzoni, Maria Bencivenga, Salvatore Siena, Andrea Sartore-Bianchi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Maria Di Bartolomeo, Annunziata Gloghini, Silvia Marsoni, Antonino Sottile, Anna Sapino, Caterina Marchio, Asa Dahle-Smith, Zosia Miedzybrodzka, Jessica Lee, Siraj M. Ali, Jeffrey S. Ross, Brian M. Alexander, Vincent A. Miller, Russell Petty, Alexa B. Schrock, Silvia Giordano
Summary: The study highlights EGFR amplification as a driving factor of aggressive behavior and poor prognosis in gastric cancer, with EGFR inhibitors showing activity in patients with EGFR copy number gain. Additionally, the combination of EGFR and mTOR inhibitors shows promise in overcoming primary resistance mechanisms.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Jian Carrot-Zhang, Xiaotong Yao, Siddhartha Devarakonda, Aditya Deshpande, Jeffrey S. Damrauer, Tiago Chedraoui Silva, Christopher K. Wong, Hyo Young Choi, Ina Felau, A. Gordon Robertson, Mauro A. A. Castro, Lisui Bao, Esther Rheinbay, Eric Minwei Liu, Tuan Trieu, David Haan, Christina Yau, Toshinori Hinoue, Yuexin Liu, Ofer Shapira, Kiran Kumar, Karen L. Mungall, Hailei Zhang, Jake June-Koo Lee, Ashton Berger, Galen F. Gao, Binyamin Zhitomirsky, Wen-Wei Liang, Meng Zhou, Sitapriya Moorthi, Alice H. Berger, Eric A. Collisson, Michael C. Zody, Li Ding, Andrew D. Cherniack, Gad Getz, Olivier Elemento, Christopher C. Benz, Josh Stuart, J. C. Zenklusen, Rameen Beroukhim, Jason C. Chang, Joshua D. Campbell, D. Neil Hayes, Lixing Yang, Peter W. Laird, John N. Weinstein, David J. Kwiatkowski, Ming S. Tsao, William D. Travis, Ekta Khurana, Benjamin P. Berman, Katherine A. Hoadley, Nicolas Robine, Matthew Meyerson, Ramaswamy Govindan, Marcin Imielinski
Summary: Alterations in the RTK/RAS/RAF pathway are a characteristic feature of lung adenocarcinoma (LUAD). A study using whole-genome sequencing of 85 cases initially identified as RPA(-) revealed that around 33% of cases were actually RPA(+). The remaining cases showed genetic mutations associated with tumor suppressor deletions and genome instability.
Article
Multidisciplinary Sciences
Bin Zhang, Shaowei Dong, Jian Wang, Tuxiong Huang, Pan Zhao, Jing Xu, Dongcheng Liu, Li Fu, Lingwei Wang, Guangsuo Wang, Chang Zou
Summary: By using 3D printed patient derived xenograft models, this study identifies a NOTCH mutation as a predictor of response to EGFR-TKI therapy in LUAD. The NOTCH4(Delta L12_16) mutation increases the occurrence in EGFR-TKI-sensitive patients and sensitizes EGFR-TKI-resistant LUAD cells to the drug. This is mediated by reduced localization of NOTCH4 and down-regulation of HES1 expression. Inhibition of the NOTCH4-HES1 pathway can reverse EGFR-TKI resistance.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Petr Makhov, Igor Bychkov, Bulat Faezov, Alexander Deneka, Alexander Kudinov, Emmanuelle Nicolas, Rohan Brebion, Eleanor Avril, Kathy Q. Cai, Leonid V. Kharin, Mark Voloshin, Elena Frantsiyants, Nikolay Karnaukhov, Oleg I. Kit, Iuliia Topchu, Rushaniya Fazliyeva, Anna S. Nikonova, Ilya G. Serebriiskii, Hossein Borghaei, Martin Edelman, Essel Dulaimi, Erica A. Golemis, Yanis Boumber
Summary: MSI2 regulates EGFR protein expression in non-small cell lung cancer, and depletion of MSI2 can affect proliferation of EGFR(mut) cells and response to EGFR-targeting drugs, suggesting inhibition of MSI2 could be clinically valuable in EGFR(mut) NSCLC.
Article
Oncology
Yiquan Xu, Jingjing Yan, Chengzhi Zhou, Lin Wu, Haibo Wang, Jun Zhao, Maolin Zhou, Jingyi Wang, Xinlong Zheng, Longfeng Zhang, Kan Jiang, Xiaobin Zheng, Qian Miao, Shiwen Wu, Zihua Zou, Rong Lian, Yuange He, Rongrong Chen, Shanshan Yang, Yujing Li, Sihui Chen, Gen Lin
Summary: This retrospective study explored the impact of EGFR copy number gain (CNG) on the efficacy of first-line EGFR-TKIs in NSCLC patients with EGFR mutation. The results showed that EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Anna Buder, Ellen Heitzer, Julie Waldispuehl-Geigl, Sabrina Weber, Tina Moser, Maximilian J. Hochmair, Klaus Hackner, Peter Errhalt, Ulrike Setinek, Martin Filipits
Summary: The presence of resistance-related gene SCNAs in plasma before the initiation of osimertinib therapy is associated with lower response rate and shorter progression-free and overall survival.
Article
Multidisciplinary Sciences
Alexander M. Frankell, Michelle Dietzen, Maise Al Bakir, Emilia L. Lim, Takahiro Karasaki, Sophia Ward, Selvaraju Veeriah, Emma Colliver, Ariana Huebner, Abigail Bunkum, Mark S. Hill, Kristiana Grigoriadis, David A. Moore, James R. M. Black, Wing Kin Liu, Kerstin Thol, Oriol Pich, Thomas B. K. Watkins, Cristina Naceur-Lombardelli, Daniel E. Cook, Roberto Salgado, Gareth A. Wilson, Chris Bailey, Mihaela Angelova, Robert Bentham, Carlos Martinez-Ruiz, Christopher Abbosh, Andrew G. Nicholson, John Le Quesne, Dhruva Biswas, Rachel Rosenthal, Clare Puttick, Sonya Hessey, Claudia Lee, Paulina Prymas, Antonia Toncheva, Jon Smith, Wei Xing, Jerome Nicod, Gillian Price, Keith M. Kerr, Babu Naidu, Gary Middleton, Kevin G. Blyth, Dean A. Fennell, Martin D. Forster, Siow Ming Lee, Mary Falzon, Madeleine Hewish, Michael J. Shackcloth, Eric Lim, Sarah Benafif, Peter Russell, Ekaterini Boleti, Matthew G. Krebs, Jason F. Lester, Dionysis Papadatos-Pastos, Tanya Ahmad, Ricky M. Thakrar, David Lawrence, Neal Navani, Sam M. Janes, Caroline Dive, Fiona H. Blackhall, Yvonne Summers, Judith Cave, Teresa Marafioti, Javier Herrero, Sergio A. Quezada, Karl S. Peggs, Roland F. Schwarz, Peter Van Loo, Daniel M. Miedema, Nicolai J. Birkbak, Crispin T. Hiley, Allan Hackshaw, Simone Zaccaria, Mariam Jamal-Hanjani, Nicholas McGranahan, Charles Swanton, Amrita Bajaj, Apostolos Nakas, Azmina Sodha-Ramdeen, Keng Ang, Mohamad Tufail, Mohammed Fiyaz Chowdhry, Molly Scotland, Rebecca Boyles, Sridhar Rathinam, Claire Wilson, Domenic Marrone, Sean Dulloo, Gurdeep Matharu, Jacqui A. Shaw, Joa Riley, Lindsay Primrose, Heather Cheyne, Mohammed Khalil, Shirley Richardson, Tracey Cruickshank, Kayleigh Gilbert, Akshay J. Patel, Aya Osman, Christer Lacson, Gerald Langman, Helen Shackleford, Madava Djearaman, Salma Kadiri, Angela Leek, Jack Davies Hodgkinson, Nicola Totten, Angeles Montero, Elaine Smith, Eustace Fontaine, Felice Granato, Helen Doran, Juliette Novasio, Kendadai Rammohan, Leena Joseph, Paul Bishop, Rajesh Shah, Stuart Moss, Vijay Joshi, Philip Crosbie, Fabio Gomes, Kate Brown, Mathew Carter, Anshuman Chaturvedi, Lynsey Priest, Pedro Oliveira, Colin R. Lindsay, Alexandra Clipson, Jonathan Tugwood, Alastair Kerr, Dominic G. Rothwell, Elaine Kilgour, Hugo J. W. L. Aerts, Tom L. Kaufmann, Zoltan Szallasi, Judit Kisistok, Mateo Sokac, Miklos Diossy, Jonas Demeulemeester, Aengus Stewart, Alastair Magness, Andrew Rowan, Angeliki Karamani, Benny Chain, Brittany B. Campbell, Carla Castignani, Clare E. Weeden, Corentin Richard, David R. Pearce, Despoina Karagianni, Dina Levi, Elena Hoxha, Elizabeth Larose Cadieux, Emma Nye, Eva Gronroos, Felip Galvez-Cancino, Foteini Athanasopoulou, Francisco Gimeno-Valiente, George Kassiotis, Georgia Stavrou, Gerasimos Mastrokalos, Haoran L. Zhai, Helen L. Lowe, Ignacio Matos, Jacki Goldman, James L. Reading, Jayant K. Rane, Jie Min Lam, John A. Hartley, Katey S. S. Enfield, Kayalvizhi Selvaraju, Kevin Litchfield, Kevin W. Ng, Kezhong Chen, Krijn Dijkstra, Krupa Thakkar, Leah Ensell, Mansi Shah, Marcos Vasquez, Maria Litovchenko, Mariana Werner Sunderland, Michelle Leung, Mickael Escudero, Miljana Tanic, Monica Sivakumar, Nnennaya Kanu, Olga Chervova, Olivia Lucas, Othman Al-Sawaf, Philip Hobson, Piotr Pawlik, Richard Kevin Stone, Robert E. Hynds, Roberto Vendramin, Sadegh Saghafinia, Saioa Lopez, Samuel Gamble, Seng Kuong Anakin Ung, Sharon Vanloo, Stefan Boeing, Stephan Beck, Supreet Kaur Bola, Tamara Denner, Thanos P. Mourikis, Victoria Spanswick, Vittorio Barbe, Wei-Ting Lu, William Hill, Yin Wu, Yutaka Naito, Zoe Ramsden, Catarina Veiga, Gary Royle, Charles-Antoine Collins-Fekete, Francesco Fraioli, Paul Ashford, Tristan Clark, Elaine Borg, James Wilson, Alexander James Procter, Asia Ahmed, Magali N. Taylor, Arjun Nair, Davide Patrini, Emilie Martinoni Hoogenboom, Fleur Monk, James W. Holding, Junaid Choudhary, Kunal Bhakhri, Marco Scarci, Martin Hayward, Nikolaos Panagiotopoulos, Pat Gorman, Reena Khiroya, Robert C. M. Stephens, Yien Ning Sophia Wong, Steve Bandula, Abigail Sharp, Sean Smith, Nicole Gower, Harjot Kaur Dhanda, Kitty Chan, Camilla Pilotti, Rachel Leslie, Anca Grapa, Hanyun Zhang, Khalid AbdulJabbar, Xiaoxi Pan, Yinyin Yuan, David Chuter, Mairead MacKenzie, Serena Chee, Aiman Alzetani, Lydia Scarlett, Jennifer Richards, Papawadee Ingram, Silvia Austin, Paulo De Sousa, Simon Jordan, Alexandra Rice, Hilgardt Raubenheimer, Harshil Bhayani, Lyn Ambrose, Anand Devaraj, Hema Chavan, Sofina Begum, Silviu Buderi, Daniel Kaniu, Mpho Malima, Sarah Booth, Nadia Fernandes, Pratibha Shah, Chiara Proli, Sarah Danson, Lily Robinson, Craig Dick, Alan Kirk, Mo Asif, Rocco Bilancia, Nikos Kostoulas, Mathew Thomas
Summary: This study analyzed 1,644 tumor regions and found various gene mutations and evolutionary processes in lung adenocarcinoma. It was discovered that clonal expansion and whole genome doubling play important roles in the development and relapse of non-small cell lung cancer. The findings also revealed similarities in etiology and pathogenesis between lung adenocarcinoma in smokers and never-smokers.
Article
Multidisciplinary Sciences
Ashley N. Hall, Tychele N. Turner, Christine Queitsch
Summary: The study investigated copy number variation of ribosomal RNA genes (rDNA) and found no differences in probands with autism spectrum disorder and unaffected siblings. Validation results suggest that the previously reported concerted copy number variation between 45S and 5S arrays may be due to variable data quality, and meaningful correlation between 45S and 5S copy numbers was not detected in various datasets.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Georgette Tanner, David R. Westhead, Alastair Droop, Lucy F. Stead
Summary: Intratumour heterogeneity provides tumors with adaptability and treatment resistance, requiring accurate clonal architecture characterization for effective cancer treatments. A lack of systematic benchmarking for subclonal deconvolution methods led the authors to simulate different tumor genomes to identify the optimal pipelines for achieving accurate results.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ji-Youn Sung, Dong-Won Park, Seung-Hyeun Lee
Summary: This study found that high TMB level is associated with adverse treatment outcomes in patients with EGFR-mutated lung cancer, suggesting that high TMB may serve as a predictive biomarker and require tailored therapeutic approaches.
Article
Multidisciplinary Sciences
Yuxuan Wang, Christopher Douville, Joshua D. Cohen, Austin Mattox, Sam Curtis, Natalie Silliman, Maria Popoli, Janine Ptak, Lisa Dobbyn, Nadine Nehme, Jonathan C. Dudley, Mahmoud Summers, Ming Zhang, Lan T. Ho-Pham, Bich N. H. Tran, Thach S. Tran, Tuan Nguyen, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W. Kinzlera, Bert Vogelsteina
Summary: The analysis of cell-free DNA (cfDNA) from plasma has great potential for early cancer detection. A new method called MethylSaferSeqS allows the evaluation of DNA molecules for changes in sequence, methylation, or copy number, increasing the sensitivity of cancer detection assays. The method involves copying both strands of each DNA-barcoded molecule and separating the original strands from the copied strands to obtain epigenetic and genetic alterations. By applying this method to plasma samples from individuals with different types of cancer, the study successfully detected expected patterns of mutations, copy number alterations, and methylation. MethylSaferSeqS has the potential to address various genetics and epigenetics-related questions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Pediatrics
Hongfang Mei, Lin Yang, Tiantian Xiao, Sujuan Wang, Bingbing Wu, Huijun Wang, Yulan Lu, Xinran Dong, Hong Yang, Wenhao Zhou
Summary: This study explored the genetic spectrum of cerebral palsy in a Chinese pediatric cohort and identified genetic variants in approximately 35.9% of patients. Patients without clinical risk factors or with a family history were more likely to have genetic risk factors.
JOURNAL OF PEDIATRICS
(2022)
Article
Oncology
P. Selenica, A. Marra, N. J. Choudhury, A. Gazzo, C. J. Falcon, J. Patel, X. Pei, Y. Zhu, C. K. Y. Ng, M. Curry, G. Heller, Y. -K. Zhang, M. F. Berger, M. Ladanyi, C. M. Rudin, S. Chandarlapaty, C. M. Lovly, J. S. Reis-Filho, H. A. Yu
Summary: This study found that APOBEC mutational signatures increase in EGFR-mutant lung cancer under the selective pressure of osimertinib. Samples with APOBEC mutational signatures had increased mutation frequency, more frequent occurrence of private mutations and large-scale genomic alterations.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Johan Staaf, Mattias Aine, Deborah F. Nacer, Maria Planck, Elsa Arbajian
Summary: This study investigated the differences in clinical characteristics, molecular alterations, and molecular phenotypes between patient populations with early-stage lung adenocarcinoma with respect to age at diagnosis. It was found that younger patients were more likely to harbor certain driver mutations. Age was also associated with certain mutational signatures, but did not affect transcriptional, copy number, or epigenetic variation in the tumors.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Ranjan Pathak, Victoria M. Villaflor
Summary: Despite the initial effectiveness of EGFR-tyrosine kinase inhibitors, resistance eventually develops in almost all patients. Histological changes in tumors are increasingly recognized as a key mechanism of resistance to EGFR-directed therapies. This article summarizes known histologic changes leading to resistance to EGFR TKIs and explores new pathways for developing effective therapies.