Résumé
Patient derived xenografts (PDXs) are increasingly appreciated models in cancer research and preclinical testing. We have established a collection of 20 breast and 20 ovarian cancer PDXs and investigated their biological and clinical characteristics, as well as their genetic stability. Take rates were distinctly lower with breast (16%) compared to ovarian cancers (85%). The majority of our breast PDX originated from triple negative (14/20), grade 3 tumors (18/20) and breast cancers with reduced recurrence free survival. Interestingly, we stabilized 1 ER-/HER2+ and 5 ER+ PDX. Overall we showed that breast tumors that gave rise to a PDX (take) showed significantly different expression profiles compared to tumors which did not take. Ovarian PDX originated all from high grade cancers, but comprised all major ovarian cancer histotypes (mucinous, clear cell, carcinosarcoma and serous carcinoma). Breast and ovarian PDXs faithfully recapitulated the histological features of their tumors of origin. The excellent conservation of original transcriptome characteristics was a further proof of the phenotypic stability shown by our PDX models. Noticeably, all grafts from ER+ cancers expressed ER at the RNA and protein levels. Array-CGH analysis revealed that PDXs presented a high degree of conservation of the Copy Number Change (CNC) profiles of the tumors they stemmed from and profiles from PDXs established from the same original tumor were highly overlapping. We determined that CNC representing up to 6% of the genome corresponded to oligoclonal events present in the tumor of origin that got gradually lost in the PDXs along passages. Furthermore, we noted that a minority of the PDXs presented a fraction of de novo occurring events representing up to 10% of the genome, suggesting limited levels of ongoing genetic instability. In conclusion, our data show that breast and ovarian cancer PDX are excellent reproductions of the tumors of origin but remain genetically dynamic elements susceptible to drift during sequential passages. Citation Format: Charles G. Theillet, Stanislas du Manoir, Beatrice Orsetti. Breast and ovarian cancer PDXs show excellent conservation of original features but are genetically plastic. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1226. doi:10.1158/1538-7445.AM2014-1226