scholarly journals FNA smears of pancreatic ductal adenocarcinoma are superior to formalin-fixed paraffin-embedded tissue as a source of DNA: Comparison of targeted KRAS amplification and genotyping in matched preresection and postresection samples

2017 ◽  
Vol 125 (11) ◽  
pp. 838-847 ◽  
Author(s):  
Christopher P. Hartley ◽  
Aparna M. Mahajan ◽  
Suzanne M. Selvaggi ◽  
William M. Rehrauer
2012 ◽  
Vol 226 (5) ◽  
pp. 756-763 ◽  
Author(s):  
Kalnisha Naidoo ◽  
Richard Jones ◽  
Branko Dmitrovic ◽  
Nilukshi Wijesuriya ◽  
Hemant Kocher ◽  
...  

2021 ◽  
Vol 147 (5) ◽  
pp. 1341-1354
Author(s):  
Yutaka Endo ◽  
Mao Fujimoto ◽  
Nanako Ito ◽  
Yoriko Takahashi ◽  
Minoru Kitago ◽  
...  

AbstractPurposeThe present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC).MethodsGenome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort.ResultsThe DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in theCDK14gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively.ConclusionThese findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 276-276
Author(s):  
Caitlin A McIntyre ◽  
Sharon Anita Lawrence ◽  
Winston Wong ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
...  

276 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. KRAS, TP53, CDKN2A and SMAD4 are established driver genes in PDAC. We aimed to determine if the mutational status of these 4 driver genes, and other frequently altered genes, are predictive of clinical outcomes in patients who undergo resection. Methods: Patients who underwent resection of PDAC and consented to targeted sequencing of their primary tumor using MSK-IMPACT, were included. Genomic alterations were determined based on MSK-IMPACT sequencing results of formalin-fixed, paraffin-embedded tumor. A prospectively maintained database and electronic medical record were queried for clinical and pathologic variables. Gene mutation status was compared with overall survival (OS) and recurrence free survival (RFS) using the log-rank test, and with pathologic variables using Wilcoxon rank-sum and Fisher’s exact tests. Results: Targeted genomic sequencing was performed on N = 285 primary tumors resected between 2004-2017. N = 55 (19%) patients received neoadjuvant therapy prior to sequencing and N = 220 (77%) received adjuvant therapy. Median OS was 39 months with a median follow up of 22 months. Frequency of genomic alterations and their association with OS and RFS are shown in Table 1. Alterations in both KRAS and TP53 were associated with worse OS, but not RFS, as compared to wildtype. Mutant KRAS was also associated with larger tumor size (median, 3.0 vs 2.2cm, p = 0.009). Conclusions: Alterations in KRAS and TP53 were associated with worse OS in patients with resected PDAC. Further analysis will include the association of driver gene variants, as well as other gene alterations, with clinical and pathologic outcomes. [Table: see text]


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