Joshua D Campbell1, Christopher Lathan2, Lynette Sholl3, Matthew Ducar4, Mikenah Vega4, Ashwini Sunkavalli4, Ling Lin4, Megan Hanna5, Laura Schubert4, Aaron Thorner4, Nicholas Faris6, David R Williams7, Raymond U Osarogiagbon6, Paul van Hummelen4, Matthew Meyerson8, Laura MacConaill9. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts2Cancer Program, Broad Institute of MIT and Harvard, Boston, Massachusetts. 2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 3. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts. 4. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 5. Cancer Program, Broad Institute of MIT and Harvard, Boston, Massachusetts. 6. Multidisciplinary Thoracic Oncology Program, Baptist Cancer Center, Memphis, Tennessee. 7. Department of Social and Behavior Sciences, Harvard T. H. Chan School of Public Health, Boston, Massachusetts7Department of African and African American Studies, Harvard University, Cambridge, Massachusetts. 8. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts2Cancer Program, Broad Institute of MIT and Harvard, Boston, Massachusetts4Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 9. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts4Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
IMPORTANCE: Lung cancer is the leading cause of cancer death in the United States in all ethnic and racial groups. The overall death rate from lung cancer is higher in black patients than in white patients. OBJECTIVE: To compare the prevalence and types of somatic alterations between lung cancers from black patients and white patients. Differences in mutational frequencies could illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients' treatment. DESIGN, SETTING, AND PARTICIPANTS: Tumor specimens were collected from Baptist Cancer Center (Memphis, Tennessee) over the course of 9 years (January 2004-December 2012). Genomic analysis by massively parallel sequencing of 504 cancer genes was performed at Dana-Farber Cancer Institute (Boston, Massachusetts). Overall, 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) were profiled from 245 black patients and 264 white patients. MAIN OUTCOMES AND MEASURES: The frequencies of genomic alterations were compared between tumors from black and white populations. RESULTS: Overall, 509 lung cancers were collected and analyzed (273 women [129 black patients; 144 white patients] and 236 men [116 black patients; 120 white patients]). Using 313 adenocarcinomas and 138 squamous cell carcinomas with genetically supported ancestry, overall mutational frequencies and copy number changes were not significantly different between black and white populations in either tumor type after correcting for multiple hypothesis testing. Furthermore, specific activating alterations in members of the receptor tyrosine kinase/Ras/Raf pathway including EGFR and KRAS were not significantly different between populations in lung adenocarcinoma. CONCLUSIONS AND RELEVANCE: These results demonstrate that lung cancers from black patients are similar to cancers from white patients with respect to clinically actionable genomic alterations and suggest that clinical trials of targeted therapies could significantly benefit patients in both groups.
IMPORTANCE: Lung cancer is the leading cause of cancer death in the United States in all ethnic and racial groups. The overall death rate from lung cancer is higher in black patients than in white patients. OBJECTIVE: To compare the prevalence and types of somatic alterations between lung cancers from black patients and white patients. Differences in mutational frequencies could illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients' treatment. DESIGN, SETTING, AND PARTICIPANTS: Tumor specimens were collected from Baptist Cancer Center (Memphis, Tennessee) over the course of 9 years (January 2004-December 2012). Genomic analysis by massively parallel sequencing of 504 cancer genes was performed at Dana-Farber Cancer Institute (Boston, Massachusetts). Overall, 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) were profiled from 245 black patients and 264 white patients. MAIN OUTCOMES AND MEASURES: The frequencies of genomic alterations were compared between tumors from black and white populations. RESULTS: Overall, 509 lung cancers were collected and analyzed (273 women [129 black patients; 144 white patients] and 236 men [116 black patients; 120 white patients]). Using 313 adenocarcinomas and 138 squamous cell carcinomas with genetically supported ancestry, overall mutational frequencies and copy number changes were not significantly different between black and white populations in either tumor type after correcting for multiple hypothesis testing. Furthermore, specific activating alterations in members of the receptor tyrosine kinase/Ras/Raf pathway including EGFR and KRAS were not significantly different between populations in lung adenocarcinoma. CONCLUSIONS AND RELEVANCE: These results demonstrate that lung cancers from black patients are similar to cancers from white patients with respect to clinically actionable genomic alterations and suggest that clinical trials of targeted therapies could significantly benefit patients in both groups.
Authors: Alkes L Price; Nick J Patterson; Robert M Plenge; Michael E Weinblatt; Nancy A Shadick; David Reich Journal: Nat Genet Date: 2006-07-23 Impact factor: 38.330
Authors: Oscar Arrieta; Andrés F Cardona; Claudio Martín; Luis Más-López; Luis Corrales-Rodríguez; Guillermo Bramuglia; Omar Castillo-Fernandez; Matthew Meyerson; Eduardo Amieva-Rivera; Alma Delia Campos-Parra; Hernán Carranza; Juan Carlos Gómez de la Torre; Yanina Powazniak; Fernando Aldaco-Sarvide; Carlos Vargas; Mariana Trigo; Manuel Magallanes-Maciel; Jorge Otero; Roberto Sánchez-Reyes; Mauricio Cuello Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609
Authors: Marcin Imielinski; Alice H Berger; Peter S Hammerman; Bryan Hernandez; Trevor J Pugh; Eran Hodis; Jeonghee Cho; James Suh; Marzia Capelletti; Andrey Sivachenko; Carrie Sougnez; Daniel Auclair; Michael S Lawrence; Petar Stojanov; Kristian Cibulskis; Kyusam Choi; Luc de Waal; Tanaz Sharifnia; Angela Brooks; Heidi Greulich; Shantanu Banerji; Thomas Zander; Danila Seidel; Frauke Leenders; Sascha Ansén; Corinna Ludwig; Walburga Engel-Riedel; Erich Stoelben; Jürgen Wolf; Chandra Goparju; Kristin Thompson; Wendy Winckler; David Kwiatkowski; Bruce E Johnson; Pasi A Jänne; Vincent A Miller; William Pao; William D Travis; Harvey I Pass; Stacey B Gabriel; Eric S Lander; Roman K Thomas; Levi A Garraway; Gad Getz; Matthew Meyerson Journal: Cell Date: 2012-09-14 Impact factor: 41.582
Authors: Norihiro Yamaguchi; Paul A Vanderlaan; Erik Folch; David H Boucher; Hannah M Canepa; Michael S Kent; Sidharta P Gangadharan; Adnan Majid; Olivier N Kocher; Michael A Goldstein; Mark S Huberman; Daniel B Costa Journal: Lung Cancer Date: 2013-08-07 Impact factor: 5.705
Authors: Joshua D Campbell; Anton Alexandrov; Jaegil Kim; Jeremiah Wala; Alice H Berger; Chandra Sekhar Pedamallu; Sachet A Shukla; Guangwu Guo; Angela N Brooks; Bradley A Murray; Marcin Imielinski; Xin Hu; Shiyun Ling; Rehan Akbani; Mara Rosenberg; Carrie Cibulskis; Aruna Ramachandran; Eric A Collisson; David J Kwiatkowski; Michael S Lawrence; John N Weinstein; Roel G W Verhaak; Catherine J Wu; Peter S Hammerman; Andrew D Cherniack; Gad Getz; Maxim N Artyomov; Robert Schreiber; Ramaswamy Govindan; Matthew Meyerson Journal: Nat Genet Date: 2016-05-09 Impact factor: 38.330
Authors: Steven S Coughlin; Patricia Matthews-Juarez; Paul D Juarez; Courtnee E Melton; Mario King Journal: Cancer Med Date: 2014-09-14 Impact factor: 4.452
Authors: Haiying Cheng; H Dean Hosgood; Lei Deng; Kenny Ye; Christopher Su; Janaki Sharma; Yuanquan Yang; Balazs Halmos; Roman Perez-Soler Journal: Clin Lung Cancer Date: 2019-07-17 Impact factor: 4.785
Authors: Eudocia Q Lee; Ugonma N Chukwueke; Shawn L Hervey-Jumper; John F de Groot; Jose Pablo Leone; Terri S Armstrong; Susan M Chang; David Arons; Kathy Oliver; Kay Verble; Al Musella; Nicole Willmarth; Brian M Alexander; Amanda Bates; Lisa Doherty; Evanthia Galanis; Sarah Gaffey; Thomas Halkin; Bret E Friday; Maryam Fouladi; Nancy U Lin; David Macdonald; Minesh P Mehta; Marta Penas-Prado; Michael A Vogelbaum; Solmaz Sahebjam; David Sandak; Martin van den Bent; Michael Weller; David A Reardon; Patrick Y Wen Journal: Neuro Oncol Date: 2019-09-06 Impact factor: 12.300
Authors: Nicholas T Gimbrone; Bhaswati Sarcar; Edna R Gordian; Jason I Rivera; Christian Lopez; Sean J Yoder; Jamie K Teer; Eric A Welsh; Alberto A Chiappori; Matthew B Schabath; Gary W Reuther; Julie Dutil; Miosotis Garcia; Ronald Ventosilla-Villanueva; Luis Vera-Valdivia; Alejandro Yabar-Berrocal; Rodrigo Motta-Guerrero; Pedro G Santiago-Cardona; Teresita Muñoz-Antonia; W Douglas Cress Journal: J Thorac Oncol Date: 2017-09-11 Impact factor: 15.609
Authors: Elisabeth I Heath; Filipa Lynce; Joanne Xiu; Angela Ellerbrock; Sandeep K Reddy; Elias Obeid; Stephen V Liu; Aliccia Bollig-Fischer; Duska Separovic; Ari Vanderwalde Journal: Anticancer Res Date: 2018-04 Impact factor: 2.480
Authors: Khadijah A Mitchell; Adriana Zingone; Leila Toulabi; Jacob Boeckelman; Bríd M Ryan Journal: Clin Cancer Res Date: 2017-12-01 Impact factor: 12.531
Authors: Jiao Yuan; Zhongyi Hu; Brandon A Mahal; Sihai D Zhao; Kevin H Kensler; Jingjiang Pi; Xiaowen Hu; Youyou Zhang; Yueying Wang; Junjie Jiang; Chunsheng Li; Xiaomin Zhong; Kathleen T Montone; Guoqiang Guan; Janos L Tanyi; Yi Fan; Xiaowei Xu; Mark A Morgan; Meixiao Long; Yuzhen Zhang; Rugang Zhang; Anil K Sood; Timothy R Rebbeck; Chi V Dang; Lin Zhang Journal: Cancer Cell Date: 2018-10-08 Impact factor: 31.743
Authors: Rony F Arauz; Jung S Byun; Mayank Tandon; Sanju Sinha; Skyler Kuhn; Sheryse Taylor; Adriana Zingone; Khadijah A Mitchell; Sharon R Pine; Kevin Gardner; Eliseo J Perez-Stable; Anna M Napoles; Bríd M Ryan Journal: J Thorac Oncol Date: 2020-09-12 Impact factor: 15.609