Integrative immunologic and genomic characterization of brain metastasis from ovarian/peritoneal cancer

被引:9
作者
Choi, Youn Jin [1 ]
Kim, Sang-Yeob [2 ]
Park, Hyeon-Chun [3 ]
Chung, Yeun-Jun [3 ,4 ]
Hur, Soo Young [1 ]
Lee, Sug Hyung [5 ,6 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Gynecol & Obstet, Seoul, South Korea
[2] Univ Ulsan, Asan Med Ctr, Asan Inst Life Sci, Coll Med, Seoul, South Korea
[3] Catholic Univ Korea, Coll Med, Integrated Res Ctr Genome Polymorphism, Seoul, South Korea
[4] Catholic Univ Korea, Coll Med, Dept Microbiol, 222 Banpo Daero, Seoul 06591, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Pathol, Banpodaero 222, Seoul 06591, South Korea
[6] Catholic Univ Korea, Coll Med, Canc Evolut Res Ctr, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Brain metastasis; Genetic alteration; Ovarian cancer; Peritoneal cancer; Programmed death ligand 1; ALIGNMENT;
D O I
10.1016/j.prp.2019.03.032
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Brain metastasis from ovarian/peritoneal cancer is a rare disease that has a dismal prognosis. And genomic alterations and immune-profiling in primary ovarian/ peritoneal cancer and brain metastatic tumor tissues have not been fully elucidated. Multiplexed immunofluorescence and whole-exome sequencing of two matched brain metastatic tumor and primary ovarian/peritoneal cancer tissues were performed. The overall density of immune infiltrates in metastatic tissues (brain) was not significantly different from those in primary cancer tissues (case 1 primary: 2.12% and case 1 metastasis: 2.22%; case 2 primary: 1.70%, and case 2 metastasis: 3.46%). Of note, however, PD-Ll expression in the metastases was higher than that in the primary tumors. We found more nonsilent mutations, cancer-related genes, loss of heterozygosity (LOH) and longer lengths of copy-number alterations (CNA) in brain metastases compared to primary ovarian/peritoneal cancers. We report immunologic and genomic profiles of primary ovarian/peritoneal cancer with brain metastasis that may not only provide useful information for understanding its pathogenesis, but also clues for further innovative therapeutic treatments for ovarian cancer.
引用
收藏
页数:5
相关论文
共 14 条
[1]   Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets [J].
Brastianos, Priscilla K. ;
Carter, Scott L. ;
Santagata, Sandro ;
Cahill, Daniel P. ;
Taylor-Weiner, Amaro ;
Jones, Robert T. ;
Van Allen, Eliezer M. ;
Lawrence, Michael S. ;
Horowitz, Peleg M. ;
Cibulskis, Kristian ;
Ligon, Keith L. ;
Tabernero, Josep ;
Seoane, Joan ;
Martinez-Saez, Elena ;
Curry, William T. ;
Dunn, Ian F. ;
Paek, Sun Ha ;
Park, Sung-Hye ;
McKenna, Aaron ;
Chevalier, Aaron ;
Rosenberg, Mara ;
Barker, Frederick G., II ;
Gill, Corey M. ;
Van Hummelen, Paul ;
Thorner, Aaron R. ;
Johnson, Bruce E. ;
Hoang, Mai P. ;
Choueiri, Toni K. ;
Signoretti, Sabina ;
Sougnez, Carrie ;
Rabin, Michael S. ;
Lin, Nancy U. ;
Winer, Eric P. ;
Stemmer-Rachamimov, Anat ;
Meyerson, Matthew ;
Garraway, Levi ;
Gabriel, Stacey ;
Lander, Eric S. ;
Beroukhim, Rameen ;
Batchelor, Tracy T. ;
Baselga, Jose ;
Louis, David N. ;
Getz, Gad ;
Hahn, William C. .
CANCER DISCOVERY, 2015, 5 (11) :1164-1177
[2]   Poor prognosis in Epstein-Barr virus-negative gastric cancer with lymphoid stroma is associated with immune phenotype [J].
Cho, Charles J. ;
Kang, Hyo Jeong ;
Ryu, Yeon-Mi ;
Park, Young Soo ;
Jeong, Hui Jeong ;
Park, Young-Mi ;
Lim, Hyun ;
Lee, Jeong Hoon ;
Song, Ho June ;
Jung, Hwoon-Yong ;
Kim, Sang-Yeob ;
Myung, Seung-Jae .
GASTRIC CANCER, 2018, 21 (06) :925-935
[3]   Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data [J].
Favero, F. ;
Joshi, T. ;
Marquard, A. M. ;
Birkbak, N. J. ;
Krzystanek, M. ;
Li, Q. ;
Szallasi, Z. ;
Eklund, A. C. .
ANNALS OF ONCOLOGY, 2015, 26 (01) :64-70
[4]   Qualimap: evaluating next-generation sequencing alignment data [J].
Garcia-Alcalde, Fernando ;
Okonechnikov, Konstantin ;
Carbonell, Jose ;
Cruz, Luis M. ;
Goetz, Stefan ;
Tarazona, Sonia ;
Dopazo, Joaquin ;
Meyer, Thomas F. ;
Conesa, Ana .
BIOINFORMATICS, 2012, 28 (20) :2678-2679
[5]   Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer [J].
Haffner, Michael C. ;
Guner, Gunes ;
Taheri, Diana ;
Netto, George J. ;
Palsgrove, Doreen N. ;
Zheng, Qizhi ;
Guedes, Liana Benevides ;
Kim, Kunhwa ;
Tsai, Harrison ;
Esopi, David M. ;
Lotan, Tamara L. ;
Sharma, Rajni ;
Meeker, Alan K. ;
Chinnaiyan, Arul M. ;
Nelson, William G. ;
Yegnasubramania, Srinivasan ;
Luo, Jun ;
Mehra, Rohit ;
Antonarakis, Emmanuel S. ;
Drake, Charles G. ;
de Marzo, Angelo M. .
AMERICAN JOURNAL OF PATHOLOGY, 2018, 188 (06) :1478-1485
[6]   An immune-active tumor microenvironment favors clinical response to ipilimumab [J].
Ji, Rui-Ru ;
Chasalow, Scott D. ;
Wang, Lisu ;
Hamid, Omid ;
Schmidt, Henrik ;
Cogswell, John ;
Alaparthy, Suresh ;
Berman, David ;
Jure-Kunkel, Maria ;
Siemers, Nathan O. ;
Jackson, Jeffrey R. ;
Shahabi, Vafa .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (07) :1019-1031
[7]   Fast and accurate short read alignment with Burrows-Wheeler transform [J].
Li, Heng ;
Durbin, Richard .
BIOINFORMATICS, 2009, 25 (14) :1754-1760
[8]   The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data [J].
McKenna, Aaron ;
Hanna, Matthew ;
Banks, Eric ;
Sivachenko, Andrey ;
Cibulskis, Kristian ;
Kernytsky, Andrew ;
Garimella, Kiran ;
Altshuler, David ;
Gabriel, Stacey ;
Daly, Mark ;
DePristo, Mark A. .
GENOME RESEARCH, 2010, 20 (09) :1297-1303
[9]   Clinical blockade of PD1 and LAG3-potential mechanisms of action [J].
Nguyen, Linh T. ;
Ohashi, Pamela S. .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (01) :45-56
[10]   Brain Metastases in Epithelial Ovarian and Primary Peritoneal Carcinoma [J].
Ratner, Elena S. ;
Toy, Eugene ;
O'Malley, David M. ;
McAlpine, Jessica ;
Rutherford, Thomas J. ;
Azodi, Masoud ;
Higgins, Susan A. ;
Schwartz, Peter E. .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2009, 19 (05) :856-859