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.
Highlights
Autopsy, derived from the Greek word autopsia meaning “to see for oneself”, is a method used since the 17th century to learn about disease and determine the cause of death [1]
Research autopsy programs have emerged as a critical tool towards understanding the biology of lethal cancer and in many instances have led to significant insights into cancer progression and treatment resistance not possible with small tumor biopsies [14,15,16]
Nucleic acid quality was analyzed in 371 different frozen tissue samples collected from 80 autopsied patients, 81% of which had been diagnosed with pancreatic cancer
Summary
Autopsy, derived from the Greek word autopsia meaning “to see for oneself”, is a method used since the 17th century to learn about disease and determine the cause of death [1]. Sequencing of the human genome has led to a revolution in understanding of cancer etiology by revealing the genetic alterations characteristic of human tumors [5,6,7], the genetic features that underlie subtypes within a primary tumor type [8,9,10,11], or the mechanisms of therapeutic resistance [12,13,14] With these advances has come a revival of interest in postmortem tissue collection because advanced stage disease is typically not accessible for study by next-generation methods in samples from living patients. Towards the goal of fully understanding these issues we leveraged our experience and resources amassed while running a cancer research autopsy program spanning more than a decade to determine the quality of nucleic acids in relation to tissue of origin, postmortem interval, normal versus neoplastic histology, primary versus metastases, and performance in downstream generation sequencing methodologies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
