Abstract B101: Molecular pathology of patient derived xenografts
Authors: Guo Sheng , Qian Wubin , Cai Jie , Zhang Likun , Wery Jean-Pierre , Li Henry 
Published: May 2016

Background. The Cancer Genome Atlas (TCGA) and many other genomic profiling of patient samples generated abundant human cancer genomic datasets of various histological types and individual patients, enabling development of molecular pathology methodology per big data fashion1-4. Patient derived xenograft (PDX) is believed to mimic patient tumors with anecdotal data, and assumed to be predictive experimental models (avatar) for human trial. There is also a need to investigate tumor pathology among different histopathology types, either patient or xenograft diseases, per “big data” approach.

Methods. We first systematically compared transcriptome expression similarity within and between specific histological types using either global or specific subsets of genes using the datasets from TCGA. We next investigated PDXs (also cell lines) using the same systemic approaches.

Results. We demonstrated the presence of highly consistent correlation in transcriptome expression within a given histology types, but more distinct between the types, establishing molecular specificity alternative to histological type based on morphology, or an alternative diagnostic approach. We performed the same systematic examination of PDXs of different histological types corresponding to the TCGA types. The similar general pattern of similarity, also somewhat reduced in degree, have been observed. These suggest the high relevance of PDX to human cancer tissues in general from “big data” perspective. In contrast, this seems generally untrue for cancer cell lines: quite similar among themselves even for different histological types, but less correlation to either TCGA or PDXs per disease type. The similarity among cell lines of all types may suggest a “new type of cancer, or tissue culture type”. Our studies also revealed certain specific correlations, with several examples: 1) colon and rectal adenocarcinoma are highly correlated, without apparent difference; 2) NSCLC SCC are quite different from NSCLC ADC, as seen morphologically; 3) NSCLC SCC are also quite closely related to HNSCC.

Conclusion. There are generally good correlation between transcriptome expression based molecular pathology and histopathology; the molecular pathology of PDXs are generally similar to that of human's, not so to human cell lines.

References

1. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202-209 (2014).

2. Hoshida, Y., et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer research 69, 7385-7392 (2009).

3. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061-1068 (2008).

4. Ge, L., et al. Integrated analysis of gene expression profile and genetic variations associated with ovarian cancer. European review for medical and pharmacological sciences 19, 2703-2710 (2015).

Citation Format: Sheng Guo, Wubin Qian, Jie Cai, Likun Zhang, Jean-Pierre Wery, Henry Li. Molecular pathology of patient derived xenografts. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B101.