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1. 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
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2. 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
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3. Supplementary Table S3 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

PancSeq protocol gene list for CLIA-certified somatic and germline analysis from whole exome sequencing data.

Published
2023
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4. Supplementary Figures 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

Supplementary Figure S1: Overview of workflow and data generation. Supplementary Figure S2: Analysis of neoplastic cellularity. Supplementary Figure S3: Recurrent copy number alterations. Supplementary Figure S4: Mutational signature analysis. Supplementary Figure S5: Analysis of PDAC gene expression signatures. Supplementary Figure S6: Clinically relevant alterations in the cohort.

Published
2023
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5. Supplementary Experimental Methods 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

Supplementary Experimental Methods

Published
2023
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6. MAF file for mutations 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 mutations identified in the cohort

Published
2023
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7. Supplementary Table S2 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

Characteristics of biopsies obtained on PancSeq protocol.

Published
2023
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8. Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

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

Subjects
Adult, Male, 0301 basic medicine, DNA Repair, MAP Kinase Signaling System, DNA repair, Germline, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Pancreatic cancer, Exome Sequencing, Carcinoma, medicine, Humans, Gene Regulatory Networks, Clinical significance, Precision Medicine, Homologous Recombination, Germ-Line Mutation, Exome sequencing, Aged, Aged, 80 and over, Sequence Analysis, RNA, business.industry, Gene Expression Profiling, Genetic Variation, Genomics, Middle Aged, medicine.disease, Precision medicine, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, business, Carcinoma, Pancreatic Ductal
Abstract

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC. Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096–111. ©2018 AACR. See related commentary by Collisson, p. 1062. This article is highlighted in the In This Issue feature, p. 1047

Published
2018
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9. Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study

Author

Alanna J. Church, Eliezer M. Van Allen, Irene Rainville, Nikhil Wagle, Elizabeth H. Stover, Levi A. Garraway, Stacy W. Gray, Frederick H. Wilson, Carol Lowenstein, Lynette M. Sholl, Vanesa Rojas-Rudilla, Andrea Garofalo, Daniel J. Treacy, Amanda Waldron, Abigail A. Santos, Steven M. Corsello, Tom C. Nguyen, Elizabeth Bair, Nelly Oliver, Sam Wood, Franklin W. Huang, Marisa W. Welch, Peter C. Lo, Pasi A. Jänne, Michael Parello, Megan J. Gorman, Steven Joffe, Marios Giannakis, Joseph P. St. Pierre, Elaine Hiller, Huma Q. Rana, Patrick Bauer, Carrie Cibulskis, Ali Amin-Mansour, Philip G. McNamara, Lauren K. Brais, Neal I. Lindeman, Christine A. Lydon, Stacey Gabriel, Judy Garber, Arezou A. Ghazani, and Jennifer C. Heng

Subjects
Adult, 0301 basic medicine, Lung Neoplasms, MEDLINE, Adenocarcinoma of Lung, Adenocarcinoma, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Databases, Genetic, Exome Sequencing, Humans, Medicine, Exome, Clinical significance, Prospective Studies, Precision Medicine, Germ-Line Mutation, Genetics (clinical), Exome sequencing, business.industry, High-Throughput Nucleotide Sequencing, Cancer, Genomics, Sequence Analysis, DNA, Precision medicine, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Personalized medicine, Colorectal Neoplasms, business
Abstract

Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples. Somatic and germ-line alterations were ranked according to therapeutic or clinical relevance. Results were interpreted using an integrated somatic and germ-line framework and returned in accordance with patient preferences. At the time of this analysis, WES had been performed and results returned to the clinical team for 165 participants. Of 768 curated somatic alterations, only 31% were associated with clinical evidence and 69% with preclinical or inferential evidence. Of 806 curated germ-line variants, 5% were clinically relevant and 56% were classified as variants of unknown significance. The variant review and decision-making processes were effective when the process was changed from that of a Molecular Tumor Board to a protocol-based approach. The development of novel interpretive and decision-support tools that draw from scientific and clinical evidence will be crucial for the success of cancer precision medicine in WES studies. Genet Med advance online publication 26 January 2017

Published
2017
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10. Assigning clinical meaning to somatic and germline whole exome sequencing data to guide cancer precision medicine

Author

Levi A. Garraway, Neal I. Lindeman, Eliezer M. Van Allen, Pasi A. Jänne, Judy Garber, Stacy W. Gray, Arezou A. Ghazani, Lynette M. Sholl, Nelly Oliver, Andrea Garofalo, Nikhil Wagle, Joseph P. St. Pierre, and Steven Joffe

Subjects
Cancer Research, Oncology, Somatic cell, business.industry, Medicine, Cancer, Meaning (existential), Precision medicine, business, Bioinformatics, medicine.disease, Exome sequencing, Germline
Abstract

11565Background: Implementing cancer precision medicine requires interpretation of each potentially clinically relevant and biologically meaningful genomic alteration to aid clinical decision-makin...

Published
2016
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