Abstract C121: Racial/ethnic differences of pediatric brain tumors in the development of orthotopic PDX models
Authors: Qi Lin , Kogiso Mari , Du Yuchen , Huang Yulun , Zhang Huiyuan , Braun Frank , Lindsay Holly , Zhao Sibo , Injac Sarah , Perlaky Lazlo , Baxter Patricia , Teo Wan-Yee , Liu Zhigang , Zhao Xiumei , Zhang Yujing , Su Jack M.F. , Li Xiao-Nan 
Published: August 2020

Brain tumor is leading cause of cancer-related death in children. While significant advances have been made in molecularly subgrouping tumors of same pathologic diagnosis, little is known about the biologic differences among racial/ethnic populations, and there is a lack of animal models that represent different racial/ethnic patients. Here, we report our analysis of tumorigenicity of a total of 215 pediatric brain tumors in SCID mice. All surgical tumor tissues were obtained from cryo lab and directly implanted into the anatomically matched locations in mouse brains, i.e., cerebral tumors (such as GBM) into mouse right cerebra, and cerebellar tumors (such as medulloblastoma) into mouse cerebella. The animals were closely monitored following institutional-approved animal protocols. Tumor formation was validated either through the harvesting of visible tumors or via histopathologic examination of paraffin-embedded whole mouse brains. From the 215 tumors, racial/ethnic information was validated in 180 tumors. Overall tumor formation was 41.2% (52/126) in white, 26.9% (7/26) in black, 50% (8/16) in more than one race, and 20% (2/5) in Asian patients. When different tumor types were compared, children with medulloblastoma exhibited similar tumor take rate, ranging from 50% (3/6) in black, to 54% (15/28) in whites and 67% (2/3) of American Indian or Alaska Native, whereas in GBM, it was 79% (11/14) in white, and 1/1 in other racial groups, and in ependymoma, it ranged from 14% (1/7) in American Indian or Alaska to 18% (4/22) in white patients. The tumor take of atypical teratoid/rhabdoid tumor (ATRT) was 63% (5/8) in white but 0% (0/3) in black patient. Low-grade gliomas (total 26) did not form xenografts, and sample size was small (&lt;5) for other types of tumors. Histopathologic and comprehensive molecular characterization of these models confirmed their replication of the original patient tumors. In summary, this study suggested the differences of tumorigenicity among different racial populations and supports the expansion of patient cohorts, particularly the minorities, to draw definitive conclusions. These orthotopic PDX models (7 from African American, 8 from American Indian/Alaska, and 1 each from more than one race and Asian) provided a novel panel of clinically relevant and racial-specific models to facilitate the biologic and preclinical studies on cancer disparities.

Note: This abstract was not presented at the conference.

Citation Format: Lin Qi, Mari Kogiso, Yuchen Du, Yulun Huang, Huiyuan Zhang, Frank Braun, Holly Lindsay, Sibo Zhao, Sarah Injac, Lazlo Perlaky, Patricia Baxter, Wan-Yee Teo, Zhigang Liu, Xiumei Zhao, Yujing Zhang, Jack M.F. Su, Xiao-Nan Li. Racial/ethnic differences of pediatric brain tumors in the development of orthotopic PDX models [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C121.