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614 results on '"Levi A. Garraway"'

1. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Author

Syed H. Zaidi, Tabitha A. Harrison, Amanda I. Phipps, Robert Steinfelder, Quang M. Trinh, Conghui Qu, Barbara L. Banbury, Peter Georgeson, Catherine S. Grasso, Marios Giannakis, Jeremy B. Adams, Elizabeth Alwers, Efrat L. Amitay, Richard T. Barfield, Sonja I. Berndt, Ivan Borozan, Hermann Brenner, Stefanie Brezina, Daniel D. Buchanan, Yin Cao, Andrew T. Chan, Jenny Chang-Claude, Charles M. Connolly, David A. Drew, Alton Brad Farris, Jane C. Figueiredo, Amy J. French, Charles S. Fuchs, Levi A. Garraway, Steve Gruber, Mark A. Guinter, Stanley R. Hamilton, Sophia Harlid, Lawrence E. Heisler, Akihisa Hidaka, John L. Hopper, Wen-Yi Huang, Jeroen R. Huyghe, Mark A. Jenkins, Paul M. Krzyzanowski, Mathieu Lemire, Yi Lin, Xuemei Luo, Elaine R. Mardis, John D. McPherson, Jessica K. Miller, Victor Moreno, Xinmeng Jasmine Mu, Reiko Nishihara, Nickolas Papadopoulos, Danielle Pasternack, Michael J. Quist, Adilya Rafikova, Emma E. G. Reid, Eve Shinbrot, Brian H. Shirts, Lincoln D. Stein, Cherie D. Teney, Lee Timms, Caroline Y. Um, Bethany Van Guelpen, Megan Van Tassel, Xiaolong Wang, David A. Wheeler, Christina K. Yung, Li Hsu, Shuji Ogino, Andrea Gsur, Polly A. Newcomb, Steven Gallinger, Michael Hoffmeister, Peter T. Campbell, Stephen N. Thibodeau, Wei Sun, Thomas J. Hudson, and Ulrike Peters

Subjects
Science
Abstract

Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Published
2020
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2. Metabolomic adaptations and correlates of survival to immune checkpoint blockade

Author

Haoxin Li, Kevin Bullock, Carino Gurjao, David Braun, Sachet A. Shukla, Dominick Bossé, Aly-Khan A. Lalani, Shuba Gopal, Chelsea Jin, Christine Horak, Megan Wind-Rotolo, Sabina Signoretti, David F. McDermott, Gordon J. Freeman, Eliezer M. Van Allen, Stuart L. Schreiber, F. Stephen Hodi, William R. Sellers, Levi A. Garraway, Clary B. Clish, Toni K. Choueiri, and Marios Giannakis

Subjects
Science
Abstract

Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival.

Published
2019
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3. Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer

Author

David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y. T. Chen, R. Katherine Alpaugh, Jean Hoffman-Censits, Levi A. Garraway, Gad Getz, Scott L. Carter, Joaquim Bellmunt, Elizabeth R. Plimack, Jonathan E. Rosenberg, and Eliezer M. Van Allen

Subjects
Science
Abstract

The impact of cisplatin-based chemotherapy on tumor genomes is complex. Here, the authors study matched pre- and post-chemotherapy primary samples in muscle-invasive bladder cancer, finding a cisplatin-based mutational signature, and highlighting the impact of intratumor heterogeneity on survival.

Published
2017
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4. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Author

Viktor A. Adalsteinsson, Gavin Ha, Samuel S. Freeman, Atish D. Choudhury, Daniel G. Stover, Heather A. Parsons, Gregory Gydush, Sarah C. Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M. Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S. Merrill, Rebecca A. Santiago, Edward P. O’Connor, Seong H. Jeong, Rachel Leeson, Rachel M. Barry, Joseph F. Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G. Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M. Oliver, Lori Marini, Adrienne G. Waks, Lauren C. Harshman, Sara M. Tolaney, Eliezer M. Van Allen, Eric P. Winer, Nancy U. Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M. Johannessen, Levi A. Garraway, Todd R. Golub, Jesse S. Boehm, Nikhil Wagle, Gad Getz, J. Christopher Love, and Matthew Meyerson

Subjects
Science
Abstract

Identifying the mutational landscape of tumours from cell-free DNA in the blood could help diagnostics in cancer. Here, the authors present ichorCNA, software that quantifies tumour content in cell free DNA, and they demonstrate that cell-free DNA whole-exome sequencing is concordant with metastatic tumour whole-exome sequencing.

Published
2017
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5. Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants

Author

Lisa Brenan, Aleksandr Andreev, Ofir Cohen, Sasha Pantel, Atanas Kamburov, Davide Cacchiarelli, Nicole S. Persky, Cong Zhu, Mukta Bagul, Eva M. Goetz, Alex B. Burgin, Levi A. Garraway, Gad Getz, Tarjei S. Mikkelsen, Federica Piccioni, David E. Root, and Cory M. Johannessen

Subjects
cancer, rare mutants, functional biology, ERK, MAPK, precision medicine, precision oncology, Biology (General), QH301-705.5
Abstract

Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants. Gain-of-function ERK2 mutants induced variable responses to RAF-, MEK-, and ERK-directed therapies, providing a reference for future treatment decisions. Tumor-associated mutations spatially clustered in two ERK2 effector-recruitment domains yet produced mutants with opposite phenotypes. This approach articulates an allele-characterization framework that can be scaled to meet the goals of genome-guided oncology.

Published
2016
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6. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

Author

Michelle Dang, Rachel E. Henderson, Levi A. Garraway, and Leonard I. Zon

Subjects
Adult zebrafish, Oral gavage, Melanoma, Vemurafenib, Medicine, Pathology, RB1-214
Abstract

Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases.

Published
2016
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7. Integrated genetic and pharmacologic interrogation of rare cancers

Author

Andrew L. Hong, Yuen-Yi Tseng, Glenn S. Cowley, Oliver Jonas, Jaime H. Cheah, Bryan D. Kynnap, Mihir B. Doshi, Coyin Oh, Stephanie C. Meyer, Alanna J. Church, Shubhroz Gill, Craig M. Bielski, Paula Keskula, Alma Imamovic, Sara Howell, Gregory V. Kryukov, Paul A. Clemons, Aviad Tsherniak, Francisca Vazquez, Brian D. Crompton, Alykhan F. Shamji, Carlos Rodriguez-Galindo, Katherine A. Janeway, Charles W. M. Roberts, Kimberly Stegmaier, Paul van Hummelen, Michael J. Cima, Robert S. Langer, Levi A. Garraway, Stuart L. Schreiber, David E. Root, William C. Hahn, and Jesse S. Boehm

Subjects
Science
Abstract

Identifying therapeutic targets in rare cancers is challenging due to the lack of relevant pre-clinical models. Here, the authors generate a cancer cell line from a paediatric patient with a rare undifferentiated sarcoma and through functional genomics and chemical screens identified CDK4 and XPO1 as potential therapeutic targets in this cancer.

Published
2016
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8. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

Author

Marios Giannakis, Xinmeng Jasmine Mu, Sachet A. Shukla, Zhi Rong Qian, Ofir Cohen, Reiko Nishihara, Samira Bahl, Yin Cao, Ali Amin-Mansour, Mai Yamauchi, Yasutaka Sukawa, Chip Stewart, Mara Rosenberg, Kosuke Mima, Kentaro Inamura, Katsuhiko Nosho, Jonathan A. Nowak, Michael S. Lawrence, Edward L. Giovannucci, Andrew T. Chan, Kimmie Ng, Jeffrey A. Meyerhardt, Eliezer M. Van Allen, Gad Getz, Stacey B. Gabriel, Eric S. Lander, Catherine J. Wu, Charles S. Fuchs, Shuji Ogino, and Levi A. Garraway

Subjects
Biology (General), QH301-705.5
Abstract

Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

Published
2016
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9. TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas

Author

Tsuyoshi Hamada, Thing Rinda Soong, Yohei Masugi, Keisuke Kosumi, Jonathan A. Nowak, Annacarolina da Silva, Xinmeng Jasmine Mu, Tyler S. Twombly, Hideo Koh, Juhong Yang, Mingyang Song, Li Liu, Mancang Gu, Yan Shi, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Sachet A. Shukla, Catherine J. Wu, Levi A. Garraway, Xuehong Zhang, Kana Wu, Jeffrey A. Meyerhardt, Andrew T. Chan, Jonathan N. Glickman, Scott J. Rodig, Gordon J. Freeman, Charles S. Fuchs, Reiko Nishihara, Marios Giannakis, and Shuji Ogino

Subjects
adaptive immunity, biomarkers, cohort studies, colorectal neoplasms, immunology, immunotherapy, molecular pathological epidemiology, survival analysis, t-lymphocytes, tumor microenvironment, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response to immunotherapy. It remains to be determined clinical, pathological, and molecular features of TIME subtypes of colorectal cancer. Using 812 colon and rectal carcinoma cases from the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association of tumor characteristics and survival outcomes with four TIME subtypes (TIME 1, CD274low/TILabsent; TIME 2, CD274high/TILpresent; TIME 3, CD274low/TILpresent; and TIME 4, CD274high/TILabsent). In survival analyses, Cox proportional hazards models were adjusted for potential confounders, including microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutation status. TIME subtypes 1, 2, 3 and 4 had 218 (27%), 117 (14%), 103 (13%), and 374 (46%) colorectal cancer cases, respectively. Compared with TIL-absent subtypes (TIME 1 and 4), TIL-present subtypes (TIME 2 and 3) were associated with high-level MSI, high-degree CIMP, BRAF mutation, and higher amounts of neoantigens (p < 0.001). TIME subtypes were not significantly associated with colorectal cancer-specific or overall survival. In conclusion, TIL-present TIME subtypes of colorectal cancer are associated with high levels of MSI and neoantigen load, supporting better responsiveness to cancer immunotherapy. Further studies examining tumor molecular alterations and additional factors in the tumor microenvironment may inform development of immunoprevention and immunotherapy strategies.

Published
2018
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10. Epigenomic Alterations in Localized and Advanced Prostate Cancer

Author

Pei-Chun Lin, Eugenia G. Giannopoulou, Kyung Park, Juan Miguel Mosquera, Andrea Sboner, Ashutosh K. Tewari, Levi A. Garraway, Himisha Beltran, Mark A. Rubin, and Olivier Elemento

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Although prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI)-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations) with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered widespread allele-specific methylation (ASM) for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease.

Published
2013
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12. The genomic landscape of prostate cancer

Author

Sylvan eBaca and Levi A. Garraway

Subjects
Genomics, prostate cancer, Cancer genomics, Genome sequencing, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Prostate cancer is a common malignancy in men, with a markedly variable clinical course. Somatic alterations in DNA drive the growth of prostate cancers and may underlie the behavior of aggressive versus indolent tumors. The accelerating application of genomic technologies over the last two decades has identified mutations that drive prostate cancer formation, progression, and therapeutic resistance. Here, we discuss exemplary somatic mutations in prostate cancer, and highlight mutated cellular pathways with biological and possible therapeutic importance. Examples include mutated genes involved in androgen signaling, cell cycle regulation, signal transduction and development. Some genetic alterations may also predict the clinical course of disease or response to therapy, although the molecular heterogeneity of prostate tumors poses challenges to genomic biomarker identification. The widespread application of massively parallel sequencing technology to the analysis of prostate cancer genomes should continue to advance both discovery-oriented and diagnostic avenues.

Published
2012
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13. Correction: Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples.

Author

Laura E. MacConaill, Catarina D. Campbell, Sarah M. Kehoe, Adam J. Bass, Charles Hatton, Lili Niu, Matt Davis, Keluo Yao, Megan Hanna, Chandrani Mondal, Lauren Luongo, Caroline M. Emery, Alissa C. Baker, Juliet Philips, Deborah J. Goff, Michelangelo Fiorentino, Mark A. Rubin, Kornelia Polyak, Jennifer Chan, Yuexiang Wang, Jonathan A. Fletcher, Sandro Santagata, Gianni Corso, Franco Roviello, Ramesh Shivdasani, Mark W. Kieran, Keith L. Ligon, Charles D. Stiles, William C. Hahn, Matthew L. Meyerson, and Levi A. Garraway

Subjects
Medicine, Science
Published
2010
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14. Correction: Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples.

Author

Laura E. MacConaill, Catarina D. Campbell, Sarah M. Kehoe, Adam J. Bass, Charles Hatton, Lili Niu, Matt Davis, Keluo Yao, Megan Hanna, Chandrani Mondal, Lauren Luongo, Caroline M. Emery, Alissa C. Baker, Juliet Philips, Deborah J. Goff, Michelangelo Fiorentino, Mark A. Rubin, Kornelia Polyak, Jennifer Chan, Yuexiang Wang, Jonathan A. Fletcher, Sandro Santagata, Gianni Corso, Franco Roviello, Ramesh Shivdasani, Mark W. Kieran, Keith L. Ligon, Charles D. Stiles, William C. Hahn, Matthew L. Meyerson, and Levi A. Garraway

Subjects
Medicine, Science
Published
2009
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15. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state

Author

Mohammad Fallahi‐Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia‐Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, and Peter K Sorger

Subjects
adaptive and reversible drug resistance, BRAFV600E melanomas, de‐differentiated NGFRHigh state, RAF and MEK inhibitors, Biology (General), QH301-705.5, Medicine (General), R5-920
Abstract

Abstract Treatment of BRAF‐mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live‐cell imaging, single‐cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug‐adapted cells up‐regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly. This phenotype is transiently stable, reverting to the drug‐naïve state within 9 days of drug withdrawal. Transcriptional profiling of cell lines and human tumors implicates a c‐Jun/ECM/FAK/Src cascade in de‐differentiation in about one‐third of cell lines studied; drug‐induced changes in c‐Jun and NGFR levels are also observed in xenograft and human tumors. Drugs targeting the c‐Jun/ECM/FAK/Src cascade as well as BET bromodomain inhibitors increase the maximum effect (Emax) of RAF/MEK kinase inhibitors by promoting cell killing. Thus, analysis of reversible drug resistance at a single‐cell level identifies signaling pathways and inhibitory drugs missed by assays that focus on cell populations.

Published
2017
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16. Supplemental Figure 9 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S9

Published
2023

17. Data from A Small Molecule That Binds and Inhibits the ETV1 Transcription Factor Oncoprotein

Author

Levi A. Garraway, Angela N. Koehler, Lucienne Ronco, Raymond Pagliarini, Douglas S. Daniels, Fallon Lin, Elizabeth K. Culyba, Cheng Zhong, Timothy A. Lewis, Emily C. Hartman, Jean-Philippe Theurillat, Colin W. Garvie, Nicolas Stransky, and Marius S. Pop

Abstract

Members of the ETS transcription factor family have been implicated in several cancers, where they are often dysregulated by genomic derangement. ETS variant 1 (ETV1) is an ETS factor gene that undergoes chromosomal translocation in prostate cancers and Ewing sarcomas, amplification in melanomas, and lineage dysregulation in gastrointestinal stromal tumors. Pharmacologic perturbation of ETV1 would be appealing in these cancers; however, oncogenic transcription factors are often deemed “undruggable” by conventional methods. Here, we used small-molecule microarray screens to identify and characterize drug-like compounds that modulate the biologic function of ETV1. We identified the 1,3,5-triazine small molecule BRD32048 as a top candidate ETV1 perturbagen. BRD32048 binds ETV1 directly, modulating both ETV1-mediated transcriptional activity and invasion of ETV1-driven cancer cells. Moreover, BRD32048 inhibits p300-dependent acetylation of ETV1, thereby promoting its degradation. These results point to a new avenue for pharmacologic ETV1 inhibition and may inform a general means to discover small molecule perturbagens of transcription factor oncoproteins. Mol Cancer Ther; 13(6); 1492–502. ©2014 AACR.

Published
2023

18. Supp. Movie 2 from Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

Author

David A. Barbie, Cloud Peter Paweletz, David Dornan, Kwok-Kin Wong, Genevieve M. Boland, Roger D. Kamm, Keith T. Flaherty, F. Stephen Hodi, Patrick A. Ott, Jochen H. Lorch, Paul T. Kirschmeier, Gordon J. Freeman, Eliezer M. Van Allen, Levi A. Garraway, Meenhard Herlyn, Juan Miret, Charles H. Yoon, Raphael Bueno, William G. Richards, Joshua Wong, Vivek Sivathanu, Thanh U. Barbie, Benchun Miao, Rohit Thummalapalli, Shunsuke Kitajima, Brian C. Miller, James M. Cleary, Sareh Parangi, Viswanath Gunda, Guilherme Rabinowits, Nicole R. LeBoeuf, Manisha Thakuria, Benjamin Izar, Parin Shah, Mei-Ju Su, Lisa Cameron, Anat O. Stemmer-Rachamimov, Jean-Pierre Eliane, Adriano Piris, Mai P. Hoang, Wei Huang, Glenn J. Hanna, Shuai Li, Hua Zhang, Eric S. Wang, Raven Vlahos, Marc R. Hammond, Tran C. Thai, Israel Cañadas, Michal Barzily-Rokni, Zhiheng Jia, Lance Stapleton, Maria Anguiano, Lauren Keogh, Robert E. Jones, Asaf Rotem, Alicia Smart, Bart Phillips, Prafulla C. Gokhale, Andrew Portell, Joshua A. Kaplan, Chandrasekar Venkataramani, Max Quinn, Ashley Merlino, Jong Wook Kim, Hans Vitzthum, Mark Bittinger, Sangeetha Palakurthi, Zhi Wei, Chaoran Cheng, Tian Tian, Gao Zhang, William Walker, Meng Xiao He, Diana Miao, Hongye Liu, Jiehui Deng, Michaela Bowden, Chensheng W. Zhou, Susanna Stinson, Elena Ivanova, Patrick H. Lizotte, Amir R. Aref, and Russell W. Jenkins

Abstract

PDOTS Movie 2

Published
2023

19. Supplementary Table 2 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

Author

Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle

Abstract

XLSX file 3569K, Change in Cancer Cell Fraction for all SNVs and Indels in All Samples

Published
2023

20. Supplementary Table S1 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

ORF overexpression screen data

Published
2023

21. MAF file for CNVs from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

MAF file for copy number variations identified in the cohort

Published
2023

22. Supplementary Figures 1 - 4 from Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Author

Jonathan E. Rosenberg, Levi A. Garraway, Alan D'Andrea, Stacey Gabriel, David B. Solit, Dean F. Bajorin, Toni K. Choueiri, Bernard H. Bochner, Philip Kantoff, Gad Getz, Michael Lawrence, Jesse Boehm, Victor Reuter, Justine A. Barletta, Sabina Signoretti, Angela Qu, Deborah Farlow, Namrata Gupta, Samira Bahl, Richard Bambury, Elizabeth A. Guancial, Jaegil Kim, Ilana Garcia-Grossman, John Sfakianos, Kevin W. O'Connor, Gregory V. Kryukov, Irina Ostrovnaya, Cong Zhu, Hikmat Al-Ahmadie, Nikhil Wagle, Gopa Iyer, Philip Kim, Kent W. Mouw, and Eliezer M. Van Allen

Abstract

Supplementary Figure 1. Mutation rates by cohort. Supplementary Figure 2. ERCC2 mutations. Supplementary Figure 3. ERCC2 mutation status and overall survival. Supplementary Figure 4. ERCC2 mutations occur in highly conserved regions.

Published
2023

23. Supplementary methods from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

Supplementary detailed methods

Published
2023

24. Supplementary Table S7 from Systematic Interrogation of 3q26 Identifies TLOC1 and SKIL as Cancer Drivers

Author

William C. Hahn, Rameen Beroukhim, Jill P. Mesirov, Pablo Tamayo, Levi A. Garraway, Barbara A. Weir, Craig H. Mermel, David A. Barbie, Nicole A. Spardy, Anna C. Schinzel, Joseph Rosenbluh, Andrew O. Giacomelli, So Young Kim, Yashaswi Shrestha, Francisca Vazquez, Hiu Wing Cheung, Rhine R. Shen, Nina Ilic, Steven E. Schumacher, Alexander Tong, and Daniel Hagerstrand

Abstract

Supplementary Table S7 - XLSX file 61K, List of shRNAs used in this study

Published
2023

26. Supp. Table S22 from Genetic Mechanisms of Immune Evasion in Colorectal Cancer

Author

Ulrike Peters, Shuji Ogino, Antoni Ribas, Charles S. Fuchs, Thomas J. Hudson, Levi A. Garraway, Eric S. Lander, Stacey B. Gabriel, Jesse M. Zaretsky, Syed H. Zaidi, Ming Yu, Catherine J. Wu, David A. Wheeler, Alexander Upfill-Brown, Jennifer Tsoi, Wei Sun, Janet L. Stanford, Sachet Shukla, Brian Shirts, Eve Shinbrot, Daniel Sanghoon Shin, Stephen J. Salipante, Ben J. Raphael, Elleanor H. Quist, Cristina Puig-Saus, Colin C. Pritchard, Matteo Pellegrini, Brian B. Nadel, Dennis J. Montoya, Mark D.M. Leiserson, Paige Krystofinski, Yeon Joo Kim, Jeroen R. Huyghe, Siwen Hu-Lieskovan, Li Hsu, William M. Grady, Milan S. Geybels, Helena Escuin-Ordinas, Charles Connolly, Gabriel Abril-Rodriguez, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Zhi Rong Qian, Reiko Nishihara, Jonathan A. Nowak, Michael Quist, Xinmeng Jasmine Mu, Tsuyoshi Hamada, Daniel K. Wells, Marios Giannakis, and Catherine S. Grasso

Abstract

Supplementary Table S22: Segmented b-allele deficits

Published
2023

27. Supplementary Table S4 from The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

Author

Dirk Schadendorf, Levi A. Garraway, Gad Getz, Scott L. Carter, Stacey B. Gabriel, Jessica C. Hassel, Benjamin Weide, Carmen Loquai, Uwe Trefzer, Carola Berking, Friederike Egberts, Helen J. Gogas, Selma Ugurel, Simone M. Goldinger, Ralf Gutzmer, Uwe Hillen, Lisa Zimmer, Deborah Farlow, Kristian Cibulskis, Aaron McKenna, Mara Rosenberg, Eran Hodis, Gregory V. Kryukov, Steven Whittaker, Amaro Taylor-Weiner, Chelsea S. Place, Eva M. Goetz, Cory M. Johannessen, Daniel J. Treacy, Antje Sucker, Nikhil Wagle, and Eliezer M. Van Allen

Abstract

PDF file, 12065K, Supplementary Table S4. Complete listing of all somatic mutations seen in all tumors. This table provides details on every non-synonymous mutation or short insertion/deletion observed in this cohort, with data on genomic coordinates, protein change, protein region affected, and read counts for each event. Many additional annotations are provided (e.g. cDNA change, RefSeq number)

Published
2023

28. Data from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor–positive (HR+) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including RB1 loss, activating alterations in AKT1, RAS, AURKA, CCNE2, ERBB2, and FGFR2, and loss of estrogen receptor expression. In vitro experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired RB1, KRAS, AURKA, or CCNE2 alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition. Three of these activating alterations—in AKT1, RAS, and AURKA—have not, to our knowledge, been previously demonstrated as mechanisms of resistance to CDK4/6i in breast cancer preclinically or in patient samples. Together, these eight mechanisms were present in 66% of resistant tumors profiled and may define therapeutic opportunities in patients.Significance:We identified eight distinct mechanisms of resistance to CDK4/6i present in 66% of resistant tumors profiled. Most of these have a therapeutic strategy to overcome or prevent resistance in these tumors. Taken together, these findings have critical implications related to the potential utility of precision-based approaches to overcome resistance in many patients with HR+ metastatic breast cancer.This article is highlighted in the In This Issue feature, p. 1079

Published
2023

29. Supplementary Table 4 from Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib

Author

Jonathan E. Rosenberg, Levi A. Garraway, Philip W. Kantoff, Stacey B. Gabriel, Eric S. Lander, David M. Sabatini, Geoffrey I. Shapiro, Massimo Loda, Sabina Signoretti, Edward C. Stack, Mary Ellen Taplin, Aymen A. Elfiky, James M. Cleary, Leena Gandhi, Toni K. Choueiri, Michelle Stewart, Jeffrey G. Supko, Susanna Jacobus, Eran Hodis, Eliezer M. Van Allen, Brian C. Grabiner, and Nikhil Wagle

Abstract

XLSX file 451K, Somatic mutations identified by whole exome sequencing

Published
2023

30. Supp. Tables S16-S19 from Genetic Mechanisms of Immune Evasion in Colorectal Cancer

Author

Ulrike Peters, Shuji Ogino, Antoni Ribas, Charles S. Fuchs, Thomas J. Hudson, Levi A. Garraway, Eric S. Lander, Stacey B. Gabriel, Jesse M. Zaretsky, Syed H. Zaidi, Ming Yu, Catherine J. Wu, David A. Wheeler, Alexander Upfill-Brown, Jennifer Tsoi, Wei Sun, Janet L. Stanford, Sachet Shukla, Brian Shirts, Eve Shinbrot, Daniel Sanghoon Shin, Stephen J. Salipante, Ben J. Raphael, Elleanor H. Quist, Cristina Puig-Saus, Colin C. Pritchard, Matteo Pellegrini, Brian B. Nadel, Dennis J. Montoya, Mark D.M. Leiserson, Paige Krystofinski, Yeon Joo Kim, Jeroen R. Huyghe, Siwen Hu-Lieskovan, Li Hsu, William M. Grady, Milan S. Geybels, Helena Escuin-Ordinas, Charles Connolly, Gabriel Abril-Rodriguez, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Zhi Rong Qian, Reiko Nishihara, Jonathan A. Nowak, Michael Quist, Xinmeng Jasmine Mu, Tsuyoshi Hamada, Daniel K. Wells, Marios Giannakis, and Catherine S. Grasso

Abstract

Supplementary Tables S16-S19, describing IHC results on NHS/HPFS data

Published
2023

31. Supplementary Table 4 from Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Author

Jonathan E. Rosenberg, Levi A. Garraway, Alan D'Andrea, Stacey Gabriel, David B. Solit, Dean F. Bajorin, Toni K. Choueiri, Bernard H. Bochner, Philip Kantoff, Gad Getz, Michael Lawrence, Jesse Boehm, Victor Reuter, Justine A. Barletta, Sabina Signoretti, Angela Qu, Deborah Farlow, Namrata Gupta, Samira Bahl, Richard Bambury, Elizabeth A. Guancial, Jaegil Kim, Ilana Garcia-Grossman, John Sfakianos, Kevin W. O'Connor, Gregory V. Kryukov, Irina Ostrovnaya, Cong Zhu, Hikmat Al-Ahmadie, Nikhil Wagle, Gopa Iyer, Philip Kim, Kent W. Mouw, and Eliezer M. Van Allen

Abstract

Significantly altered genes in clinical subsets. MutSigCV ranked lists for significantly mutated genes in the non-responders only (n = 25), the responders only (n = 25), and the ERCC2WT responders only (n = 16).

Published
2023

32. Supplementary Table 2 from Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Author

Jonathan E. Rosenberg, Levi A. Garraway, Alan D'Andrea, Stacey Gabriel, David B. Solit, Dean F. Bajorin, Toni K. Choueiri, Bernard H. Bochner, Philip Kantoff, Gad Getz, Michael Lawrence, Jesse Boehm, Victor Reuter, Justine A. Barletta, Sabina Signoretti, Angela Qu, Deborah Farlow, Namrata Gupta, Samira Bahl, Richard Bambury, Elizabeth A. Guancial, Jaegil Kim, Ilana Garcia-Grossman, John Sfakianos, Kevin W. O'Connor, Gregory V. Kryukov, Irina Ostrovnaya, Cong Zhu, Hikmat Al-Ahmadie, Nikhil Wagle, Gopa Iyer, Philip Kim, Kent W. Mouw, and Eliezer M. Van Allen

Abstract

All alterations in responders and non-responders. All somatic mutations and short insertion/deletions are listed, with additional annotations regarding genomic coordinates, protein change, allelic fractions, and validation status (if available).

Published
2023

33. Supplemental Figure 8 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S8

Published
2023

35. Supplementary Figures 1-12 from Reactivation of ERK Signaling Causes Resistance to EGFR Kinase Inhibitors

Author

Pasi A. Jänne, Kwok-Kin Wong, Nathanael S. Gray, Neal Rosen, Matthew J. Lazzara, Levi A. Garraway, Anthony Letai, Eva M. Goetz, Ophélia Maertens, Marzia Capelletti, Claire Repellin, Andrew Rogers, Madhavi Tadi, Elena V. Ivanova, Lynette Sholl, Takeshi Shimamura, Mohit Butaney, Joan Montero, Christine A. Pratilas, Calixte S. Monast, Masahiko Yanagita, Chunxiao Xu, and Dalia Ercan

Abstract

PDF file - 1.3MB, Supplementary data on MAPK1 copy number and expression, combination treatment with WZ4002 and PI3K inhibitors, impact of MEK1 K57N on WZ4002 sensitivity, Mapk1 copy number analyses and NF1 and dusp expression in drug sensitive and resistant mouse tumors

Published
2023

36. Supplemental Figure 5 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S5

Published
2023

37. Supplemental Figure 4 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S4

Published
2023

38. Supplementary Figure S5 from Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations

Author

Ryan B. Corcoran, Levi A. Garraway, Jeffrey A. Engelman, A. John Iafrate, Dora Dias-Santagata, Gad Getz, Mari Mino-Kenudson, Tiffany G. Huynh, Niall J. Lennon, Lisa M. Green, Kristin Anderka, Samira Bahl, Joseph M. Gurski, Anuj Kalsy, Elizabeth L. Lockerman, Craig H. Mermel, Kerry D. Lynch, Koki Nishimura, Jason T. Godfrey, Jason E. Faris, Eunice L. Kwak, Nikhil Wagle, Eliezer M. Van Allen, Erin M. Sennott, and Leanne G. Ahronian

Abstract

Supplementary Figure S5. Role of ARAF Q489L and MEK F53L in resistance.

Published
2023

39. Supplementary Figures S1 - S5 from Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting

Author

William C. Hahn, Aviad Tsherniak, David E. Root, Matthew Meyerson, Todd R. Golub, Charles W. Roberts, Kimberly Stegmaier, Levi A. Garraway, Glenn S. Cowley, Gregory Kryukov, Coyin Oh, Andrew D. Cherniack, Amy Goodale, Yenarae Lee, Sasha Pantel, Guozhi Jiang, Levi D. Ali, Han Xu, Stanley Gill, Maria Kost-Alimova, Mihir B. Doshi, William F. Harrington, Gavin Ha, April Cook, Uri Ben-David, Cheng-Zhong Zhang, Francisca Vazquez, Barbara A. Weir, Robin M. Meyers, and Andrew J. Aguirre

Abstract

Supplementary Figure S1. Genome-scale CRISPR-Cas9 screening identifies a strong correlation between copy number and sensitivity to CRISPR-Cas9 genome editing. Supplementary Figure S2. Global summary of the relationship of CRISPR-Cas9 guide scores to genomic copy number for all 33 cell lines screened. Supplementary Figure S3. Amplified genes represent the strongest perceived dependencies in pooled CRISPR-Cas9 screening data. Figure S4. Evaluation of the influence of copy number on CRISPR-Cas9 dependency scores in published data from Hart et al. (25). Figure S5. Representative examples of structural variations leading to copy number amplification underlying the gene-independent anti-proliferative response to CRISPRCas9 targeting of loci within these regions.

Published
2023

40. Table S2 from Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

Author

David A. Barbie, Cloud Peter Paweletz, David Dornan, Kwok-Kin Wong, Genevieve M. Boland, Roger D. Kamm, Keith T. Flaherty, F. Stephen Hodi, Patrick A. Ott, Jochen H. Lorch, Paul T. Kirschmeier, Gordon J. Freeman, Eliezer M. Van Allen, Levi A. Garraway, Meenhard Herlyn, Juan Miret, Charles H. Yoon, Raphael Bueno, William G. Richards, Joshua Wong, Vivek Sivathanu, Thanh U. Barbie, Benchun Miao, Rohit Thummalapalli, Shunsuke Kitajima, Brian C. Miller, James M. Cleary, Sareh Parangi, Viswanath Gunda, Guilherme Rabinowits, Nicole R. LeBoeuf, Manisha Thakuria, Benjamin Izar, Parin Shah, Mei-Ju Su, Lisa Cameron, Anat O. Stemmer-Rachamimov, Jean-Pierre Eliane, Adriano Piris, Mai P. Hoang, Wei Huang, Glenn J. Hanna, Shuai Li, Hua Zhang, Eric S. Wang, Raven Vlahos, Marc R. Hammond, Tran C. Thai, Israel Cañadas, Michal Barzily-Rokni, Zhiheng Jia, Lance Stapleton, Maria Anguiano, Lauren Keogh, Robert E. Jones, Asaf Rotem, Alicia Smart, Bart Phillips, Prafulla C. Gokhale, Andrew Portell, Joshua A. Kaplan, Chandrasekar Venkataramani, Max Quinn, Ashley Merlino, Jong Wook Kim, Hans Vitzthum, Mark Bittinger, Sangeetha Palakurthi, Zhi Wei, Chaoran Cheng, Tian Tian, Gao Zhang, William Walker, Meng Xiao He, Diana Miao, Hongye Liu, Jiehui Deng, Michaela Bowden, Chensheng W. Zhou, Susanna Stinson, Elena Ivanova, Patrick H. Lizotte, Amir R. Aref, and Russell W. Jenkins

Abstract

In vitro kinase inhibitory activity of Compound 1

Published
2023

41. Supplementary Table S1 from Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations

Author

Ryan B. Corcoran, Levi A. Garraway, Jeffrey A. Engelman, A. John Iafrate, Dora Dias-Santagata, Gad Getz, Mari Mino-Kenudson, Tiffany G. Huynh, Niall J. Lennon, Lisa M. Green, Kristin Anderka, Samira Bahl, Joseph M. Gurski, Anuj Kalsy, Elizabeth L. Lockerman, Craig H. Mermel, Kerry D. Lynch, Koki Nishimura, Jason T. Godfrey, Jason E. Faris, Eunice L. Kwak, Nikhil Wagle, Eliezer M. Van Allen, Erin M. Sennott, and Leanne G. Ahronian

Abstract

Supplementary Table S1. Patient characteristics and MAPK pathway reactivating resistance mechanisms of BRAF-mutant CRC patients with clinical acquired resistance to RAF/EGFR or RAF/MEK inhibitor combinations.

Published
2023

42. Supplementary Table 6 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

Author

Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle

Abstract

XLSX file 31K, Coverage and Metrics

Published
2023

43. Supplemental Table 1 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 1

Published
2023

44. Supplementary Figure 2 from Systematic Interrogation of 3q26 Identifies TLOC1 and SKIL as Cancer Drivers

Author

William C. Hahn, Rameen Beroukhim, Jill P. Mesirov, Pablo Tamayo, Levi A. Garraway, Barbara A. Weir, Craig H. Mermel, David A. Barbie, Nicole A. Spardy, Anna C. Schinzel, Joseph Rosenbluh, Andrew O. Giacomelli, So Young Kim, Yashaswi Shrestha, Francisca Vazquez, Hiu Wing Cheung, Rhine R. Shen, Nina Ilic, Steven E. Schumacher, Alexander Tong, and Daniel Hagerstrand

Abstract

Supplementary Figure 2 - PDF file 17K, SKIL induces Matrigel invasion

Published
2023

46. Supplementary Table S4 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

Treatment history for patients enrolled on the PancSeq protocol.

Published
2023

47. Supplemental Figure 7 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S7

Published
2023

48. Supplemental Table 2 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 2

Published
2023

49. Supplementary Table 4 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

Author

Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle

Abstract

XLSX file 12K, Candidate Resistance Genes from RNAi and ORF Functional Screens

Published
2023

50. Supplementary Table 5 from Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Author

Jonathan E. Rosenberg, Levi A. Garraway, Alan D'Andrea, Stacey Gabriel, David B. Solit, Dean F. Bajorin, Toni K. Choueiri, Bernard H. Bochner, Philip Kantoff, Gad Getz, Michael Lawrence, Jesse Boehm, Victor Reuter, Justine A. Barletta, Sabina Signoretti, Angela Qu, Deborah Farlow, Namrata Gupta, Samira Bahl, Richard Bambury, Elizabeth A. Guancial, Jaegil Kim, Ilana Garcia-Grossman, John Sfakianos, Kevin W. O'Connor, Gregory V. Kryukov, Irina Ostrovnaya, Cong Zhu, Hikmat Al-Ahmadie, Nikhil Wagle, Gopa Iyer, Philip Kim, Kent W. Mouw, and Eliezer M. Van Allen

Abstract

Damaging scores for alterations. This table shows the damaging scores (Methods) for nonsynonymous alterations (missense, nonsense, splice site, frame shift) studied in this cohort. The damaging score was derived as follows: missense mutations were scored using the Polyphen2 score(41) for the amino acid substitution. Nonsense mutations, splice site mutations, and short insertion/deletions were automatically assigned a damaging score of 1. "Unavailable" damaging scores are those that are missense mutations without a PolyPhen2 score.

Published
2023

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