دورية أكاديمية
Establishment and characterization of patient-derived xenograft of a rare pediatric anaplastic pleomorphic xanthoastrocytoma (PXA) bearing a CDC42SE2-BRAF fusion
| العنوان: | Establishment and characterization of patient-derived xenograft of a rare pediatric anaplastic pleomorphic xanthoastrocytoma (PXA) bearing a CDC42SE2-BRAF fusion |
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| المؤلفون: | Damayanti, Nur P., Saadatzadeh, M. Reza, Dobrota, Erika, Ordaz, Josue D., Bailey, Barbara J., Pandya, Pankita H., Bijangi-Vishehsaraei, Khadijeh, Shannon, Harlan E., Alfonso, Anthony, Coy, Kathy, Trowbridge, Melissa, Sinn, Anthony L., Zhang, Zhong-Yin, Gallagher, Rosa I., Wulfkuhle, Julia, Petricoin, Emanuel, Richardson, Angela M., Marshall, Mark S., Lion, Alex, Ferguson, Michael J., Balsara, Karl E., Pollok, Karen E. |
| المساهمون: | Christian’s Flash to a Cure, ACS-IRG, NICHD/NIH Specialized Centers in Research in Pediatric Developmental Pharmacology, NCI/NIH R01, NCI/NIH Cancer Center Support Grant |
| المصدر: | Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | Pleomorphic xanthoastrocytoma (PXA) is a rare subset of primary pediatric glioma with 70% 5-year disease free survival. However, up to 20% of cases present with local recurrence and malignant transformation into more aggressive type anaplastic PXA (AXPA) or glioblastoma. The understanding of disease etiology and mechanisms driving PXA and APXA are limited, and there is no standard of care. Therefore, development of relevant preclinical models to investigate molecular underpinnings of disease and to guide novel therapeutic approaches are of interest. Here, for the first time we established, and characterized a patient-derived xenograft (PDX) from a leptomeningeal spread of a patient with recurrent APXA bearing a novel CDC42SE2-BRAF fusion. An integrated -omics analysis was conducted to assess model fidelity of the genomic, transcriptomic, and proteomic/phosphoproteomic landscapes. A stable xenoline was derived directly from the patient recurrent tumor and maintained in 2D and 3D culture systems. Conserved histology features between the PDX and matched APXA specimen were maintained through serial passages. Whole exome sequencing (WES) demonstrated a high degree of conservation in the genomic landscape between PDX and matched human tumor, including small variants (Pearson’s r = 0.794–0.839) and tumor mutational burden (~ 3 mutations/MB). Large chromosomal variations including chromosomal gains and losses were preserved in PDX. Notably, chromosomal gain in chromosomes 4–9, 17 and 18 and loss in the short arm of chromosome 9 associated with homozygous 9p21.3 deletion involving CDKN2A/B locus were identified in both patient tumor and PDX sample. Moreover, chromosomal rearrangement involving 7q34 fusion; CDC42SE-BRAF t (5;7) (q31.1, q34) (5:130,721,239, 7:140,482,820) was identified in the PDX tumor, xenoline and matched human tumor. Transcriptomic profile of the patient’s tumor was retained in PDX (Pearson r = 0.88) and in xenoline (Pearson r = 0.63) as well as preservation of enriched signaling pathways (FDR ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-023-36107-2 |
| الإتاحة: | https://doi.org/10.1038/s41598-023-36107-2Test https://www.nature.com/articles/s41598-023-36107-2.pdfTest https://www.nature.com/articles/s41598-023-36107-2Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.77037F63 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-023-36107-2 |
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