Quantification of nucleic acid quality in postmortem tissues from a cancer research autopsy program.
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.
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Jun
J
Fan
Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Raya
R
Khanin
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Hitomi
H
Sakamoto
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Yi
Y
Zhong
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Chelsea
C
Michael
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Derwin
D
Pena
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Breanna
B
Javier
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Laura D
LD
Wood
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.|Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.|David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Christine A
CA
Iacobuzio-Donahue
D001344:Autopsy; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D009696:Nucleic Acids / Q000737:chemistry*; D010338:Pathology, Clinical / Q000592:standards*; D020871:RNA Stability
D009696:Nucleic Acids
RNA; RNA sequencing; autopsy; metastasis; post-mortem