Manaswi Gupta

Integrative clinical genomics of advanced prostate cancer

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

Oncotator: cancer variant annotation tool.

Oncotator is a tool for annotating genomic point mutations and short nucleotide insertions/deletions (indels) with variant‐ and gene‐centric information relevant to cancer researchers. This information is drawn from 14 different publicly available resources that have been pooled and indexed, and we provide an extensible framework to add additional data sources. Annotations linked to variants range from basic information, such as gene names and functional classification (e.g. missense), to cancer‐specific data from resources such as the Catalogue of Somatic Mutations in Cancer (COSMIC), the Cancer Gene Census, and The Cancer Genome Atlas (TCGA). For local use, Oncotator is freely available as a python module hosted on Github (https://github.com/broadinstitute/oncotator). Furthermore, Oncotator is also available as a web service and web application at http://www.broadinstitute.org/oncotator/.

Erratum: Integrative Clinical Genomics of Advanced Prostate Cancer

Dan Robinson, Eliezer M. Van Allen, Yi-Mi Wu, Nikolaus Schultz, Robert J. Lonigro, Juan-Miguel Mosquera, Bruce Montgomery, Mary-Ellen Taplin, Colin C. Pritchard, Gerhardt Attard, Himisha Beltran, Wassim Abida, Robert K. Bradley, Jake Vinson, Xuhong Cao, Pankaj Vats, Lakshmi P. Kunju, Maha Hussain, Felix Y. Feng, Scott A. Tomlins, Kathleen A. Cooney, David C. Smith, Christine Brennan, Javed Siddiqui, Rohit Mehra, Yu Chen, Dana E. Rathkopf, Michael J. Morris, Stephen B. Solomon, Jeremy C. Durack, Victor E. Reuter, Anuradha Gopalan, Jianjiong Gao, Massimo Loda, Rosina T. Lis, Michaela Bowden, Stephen P. Balk, Glenn Gaviola, Carrie Sougnez, Manaswi Gupta, Evan Y. Yu, Elahe A. Mostaghel, Heather H. Cheng, Hyojeong Mulcahy, Lawrence D. True, Stephen R. Plymate, Heidi Dvinge, Roberta Ferraldeschi, Penny Flohr, Susana Miranda, Zafeiris Zafeiriou, Nina Tunariu, Joaquin Mateo, Raquel Perez-Lopez, Francesca Demichelis, Brian D. Robinson, Andrea Sboner, Marc Schiffman, David M. Nanus, Scott T. Tagawa, Alexandros Sigaras, Kenneth W. Eng, Olivier Elemento, Andrea Sboner, Elisabeth I. Heath, Howard I. Scher, Kenneth J. Pienta, Philip Kantoff, Johann S. de Bono, Mark A. Rubin, Peter S. Nelson, Levi A. Garraway, Charles L. Sawyers,* and Arul M. Chinnaiyan* *Correspondence: sawyersc@mskcc.org (C.L.S.), arul@umich.edu (A.M.C.) http://dx.doi.org/10.1016/j.cell.2015.06.053

A Global Cancer Project Map Integrating Global Cancer Statistics to Guide International Efforts

Abstract 39Background:In response to the growing burden of cancer, Global Oncology, Inc., and the National Cancer Institute Center for Global Health launched a free, online, interactive map, the Global Cancer Project Map (GCPM) [http://gcpm.globalonc.org], to allow policy makers, researchers, and civil society around the world to search this central repository of international cancer control and research projects. The GCPM serves to catalyze collaboration in cancer research and clinical care, as well as inform research and care gaps.Methods:In addition to search options by project attributes, the GCPM provides map overlays of epidemiological measures using IARC’s GLOBOCAN cancer-specific estimates of incidence, prevalence, and mortality, cancer disability--adjusted life years, and UN Human Development Index country values. Currently, the map displays projects with international collaborators collated from the NCI, NCI-Designated Cancer Centers, UICC and ASCO.Results:The GCPM search options offer countless...

Launching an Interactive Cancer Projects Map: A Collaborative Approach to Global Cancer Research and Program Development

Ami S. Bhatt F.W.H. and A.S.B. contributed equally to this work. Corresponding author: Ami S. Bhatt, MD, PhD, Departments of Medicine and Genetics, Center for Innovation in Global Health, Stanford University, 269 Campus Dr, Stanford, CA 94305; e-mail: asbhatt@stanford.edu Despite living in a connected world, many research projects are developed with a so-called “convenience bias,” resulting in partnerships based on existing professional networks and collaborations. In addition, community-based cancer control programs are often implemented independently to address specific urgent and existing needs. Consequently, these projects and programs do not benefit as much as they could from best practices and protocols developed through other long-term engagements. As the global burden of cancer increases, cancer researchers and program managers are likely to benefit from a more complete understanding of ongoing work in cancer control. The limited availability of tools for collaboration and sharing of best practices have resulted in a call to action for the scientific community to partner on the development of a platform that provides knowledge of existing resources and expertise.