Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study Journal Article


Authors: Fulmer, C. G.; Park, K.; Dilcher, T.; Ho, M.; Mirabelli, S.; Alperstein, S.; Hissong, E. M.; Pittman, M.; Siddiqui, M.; Heymann, J. J.; Yantiss, R. K.; Borczuk, A. C.; Fernandes, H.; Sigel, C.; Song, W.; Mosquera, J. M.; Rao, R.
Article Title: Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study
Abstract: Background: Endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) is a sensitive and specific tool in the risk stratification of pancreatic lesions, including cysts. The sensitivity and specificity of EUS-FNA has been shown to improve when cytology is combined with next-generation sequencing (NGS). Ideally, fresh cyst fluid is used for NGS. In this pilot study, we explore the possibility of sequencing DNA derived from residual alcohol-fixed pancreatic aspirates. Methods: Residual cytologic fixatives (n = 42) from 39 patients who underwent EUS-FNA for pancreatic lesions were collected along with demographics, imaging, and laboratory studies. Samples were designated as nonneoplastic/nonmucinous benign (NB), mucinous cyst (MC), pancreatic ductal adenocarcinoma (PDAC), or well-differentiated neuroendocrine tumor (NET) on the basis of cytopathologic evaluation and sequenced on the Oncomine platform (ThermoFisher Scientific, Waltham, Massachusetts). Results: Ten of 14 (71.4%) MCs exhibited clinically significant variants, including KRAS, GNAS, and TP53. Ten of 15 (66.7%) PDACs had KRAS alterations, and 9 of 15 (60%) showed variants in TP53. No variants were detected in any NETs. Only 1 of 9 (11.1%) NB aspirates showed variants in KRAS and MAP2K. Sequencing of formalin-fixed, paraffin-embedded tissue revealed variants identical to those detected in fixative-derived DNA in 4 of 5 cases (80%). Conclusion: Residual DNA from alcohol-fixed aspirates are an underutilized source for NGS. Sequencing residual fixative-derived DNA has the potential to be integrated into the workup of pancreatic aspirates, possibly impacting management. © 2020 American Cancer Society
Keywords: sequence analysis; pancreatic neoplasms; dna; pancreatic ductal carcinoma; pancreatic carcinoma; endoscopic ultrasound-guided fine needle aspiration
Journal Title: Cancer Cytopathology
Volume: 128
Issue: 11
ISSN: 1934-662X
Publisher: John Wiley & Sons  
Date Published: 2020-11-01
Start Page: 840
End Page: 851
Language: English
DOI: 10.1002/cncy.22315
PUBMED: 32598087
PROVIDER: scopus
PMCID: PMC9285651
DOI/URL:
Notes: Article -- Export Date: 1 December 2020 -- Source: Scopus
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  1. Carlie Selbo Sigel
    116 Sigel