Abstract 504: Quantification of nucleic acid quality in postmortem tissues from a cancer research autopsy program

Abstract The last decade has seen a marked rise in the use of cancer tissues obtained from research autopsies. Such resources have been invaluable for studying cancer evolution or the mechanisms of therapeutic resistance to targeted therapies. Degradation of biomolecules is a potential challenge to usage of cancer tissues obtained in the post-mortem setting and remains incompletely studied. We analysed the nucleic acid quality in 371 different frozen tissue samples collected from 80 patients who underwent a research autopsy, including eight normal tissue types, primary and metastatic tumors. Our results indicate that RNA integrity number (RIN) of normal tissues decline with the elongation of post-mortem interval (PMI) in a tissue-type specific manner. Unlike normal tissues, the RNA quality of cancer tissues is highly variable with respect to post-mortem interval. The kinetics of DNA damage also has tissue type-specific features. Moreover, while DNA degradation is an indicator of low RNA quality, the converse is not true. Finally, we show that despite RIN values as low as 5.0, robust data can be obtained by RNA sequencing that reliably discriminates expression signatures. Based on this promising pilot data, we are currently identifying samples for multiregion RNA sequencing of pancreatic cancers with divergent morphologies within the primary and/or metastatic sites. Thus far we have screened 554 RNA samples from 10 autopsy cases. These samples represent 198 geographically distinct regions of tumor with duplicate or triplicate RNA extractions. The number of samples per patient ranges from 17 to 86 with an average of 55. Our data shows that high quality RNA can be acquired from cases with long PMI (>48h). While extensive screening of samples is required to identify those with optimal quality, the downstream data produced is of high quality and can support novel hypotheses or validations of experimental data. Citation Format: Jun Fan, Raya Khanin, Hitomi Sakamoto, Yi Zhong, Chelsea Michael, Derwin Pena, Breanna Javier, Laura Wood, Christine Iacobuzio-Donahue. Quantification of nucleic acid quality in postmortem tissues from a cancer research autopsy program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 504. doi:10.1158/1538-7445.AM2017-504