scholarly journals Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gahee Park ◽  
Joo Kyung Park ◽  
Dae-Soon Son ◽  
Seung-Ho Shin ◽  
Yeon Jeong Kim ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Gabriella Cirmena ◽  
Anna Garuti ◽  
Marilena De Mariano ◽  
Simona Coco ◽  
Lorenzo Ferrando ◽  
...  

In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, there is an unmet need for noninvasive predictive biomarkers of response. The analysis of circulating tumor DNA (ctDNA) in particular has been the object of several reports, but few of them have studied the applicability of tagged targeted deep sequencing (tTDS) to clinical practice and its performance compared with droplet digital PCR (ddPCR). Here, we present the first results from an ongoing study involving a prospectively accrued, monocentric cohort of patients affected by invasive breast cancer, undergoing neoadjuvant chemotherapy followed by surgery with curative intent as per clinical practice. A pretreatment tumor biopsy and plasma samples were collected before and during treatment, after surgery, and every six months henceforth or until relapse, whichever came first. Pretreatment biopsies were sequenced with a 409-gene massive parallel sequencing (MPS) panel, allowing the identification of target mutations and their research in plasma by tTDS and ddPCR as a complementary approach. Using tTDS, we demonstrated the presence of at least one deleterious mutation in all the relapsed cases we studied (n = 4), with an average lead time of six months before clinical relapse. The association with ddPCR was suboptimal, and only one relapsed patient could be identified with such method. tTDS shows potential as an early noninvasive method for the detection of MRD in BC patients.


Oncotarget ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 2076-2085 ◽  
Author(s):  
Andreas W. Berger ◽  
Daniel Schwerdel ◽  
Thomas J. Ettrich ◽  
Alexander Hann ◽  
Stefan A. Schmidt ◽  
...  

2016 ◽  
Vol 23 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Daniel Pietrasz ◽  
Nicolas Pécuchet ◽  
Fanny Garlan ◽  
Audrey Didelot ◽  
Olivier Dubreuil ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 288-288 ◽  
Author(s):  
Julia S. Johansen ◽  
Cecile Rose T. Vibat ◽  
Dan Calatayud ◽  
Benny Vittrup Jensen ◽  
Jane Preuss Hasselby ◽  
...  

288 Background: Non-resectable pancreatic cancer patients have a wide range of median time for overall survival (OS). Currently there is a lack of diagnostic tools to predict patient outcome at diagnosis. KRAS mutations are present in the vast majority of pancreatic tumors. The study objective was to determine if quantitative baseline and longitudinal monitoring of KRAS mutations from plasma circulating tumor DNA (ctDNA) could be used to stratify patients for predicting outcome. Methods: Plasma was prospectively collected from the Danish BIOPAC study for non-resectable pancreatic cancer patients undergoing treatment with gemcitabine or FOLFIRINOX. Feasibility of monitoring ctDNA KRAS mutations was assessed in 10 patients with long OS (median 493 days; range 360-1031) and 10 patients with short OS (median 66 days; range 21-136). KRAS G12A/C/D/R/S/V, and G13D mutations were PCR enriched, sequenced by massively parallel deep sequencing, quantitated and standardized by reporting number of copies detected per 105 genome equivalents (GE). Results: In a pilot study of 20 patients, all 18 patients with evaluable DNA had detectable KRAS mutations. Of 18 patients, 12 had baseline plus longitudinal time points (7 short, 5 long OS). Mutant KRAS copies were higher for short OS (median=994; range 0-34305 copies/105 GE) vs. with long OS (median 196; range, 34-278 copies/105 GE). Longitudinally, KRAS mutation levels remained mostly low with long OS (last time point median 204; range 8-873 copies/105 GE) vs. short OS where levels increased or remained high (median 2363; range 71-47919 copies/105 GE). Identical KRAS mutations were consistently detected for a given patient with short OS. However, long OS patients had variable KRAS mutations in longitudinal analysis. Conclusions: High levels of ctDNA KRAS mutations at diagnosis and post-treatment elevation of KRAS mutations were more associated with short OS. Different levels of KRAS mutation at diagnosis may predict patient outcome and could reflect distinct underlying tumor biology. Expansion of this prospective-retrospective biomarker cohort will be reported.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19083-e19083
Author(s):  
Junji Uchida ◽  
Kikuya Kato ◽  
Yoji Kukita ◽  
Toru Kumagai ◽  
Kazumi Nishino ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeon Jeong Kim ◽  
Yumi Kang ◽  
Jun Seop Kim ◽  
Hyun Hwan Sung ◽  
Hwang Gyun Jeon ◽  
...  

AbstractWe evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.


Sign in / Sign up

Export Citation Format

Share Document