A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative

Pishvaian, Michael J.; Bender, R Joseph; Matrisian, Lynn M.; Rahib, Lola; Hendifar, Andrew Eugene; Hoos, William; Mikhail, Sam; Chung, Vincent; Picozzi, Vincent J.; Heartwell, Craig; Mason, Kimberly; Varieur, Katelyn; Aberra, Metasebia; Madhavan, Subha; Petricoin, Emanuel; Brody, Jonathan R.

doi:10.18632/oncotarget.13225

Cited by 57 publications

(53 citation statements)

References 30 publications

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“…None of the KRAS mutations from the seven patients with KRAS mutant primary tumors were detected in the ccfDNA at the time of diagnosis, while mutations in other genes were detected. Mutant KRAS ccfDNA was, however, found by others in 10 of 34 pancreatic patients (29%) [22] or in 136 of 188 (72.3%) of patients with metastatic PDAC [23]. Another study showed that mutant KRAS ccfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively [20].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed detection of EGFR T790M mutant DNA in the circulation of cancer patients was improved by selecting for shorter DNA fragment lengths [26]. Comparisons of tumor tissue somatic DNA and ccfDNA mutation rate can be impacted by the application of different sequencing technologies and amplicon sizes [27, 28] as well as read depths and these technical issues may bias the data interpretation [22]. To avoid this pitfall we used a platform that is adapted to the detection of short DNA fragments found as circulating cell-free DNA.…”

Section: Discussionmentioning

confidence: 99%

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Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

et al. 2017

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Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA whilst 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

et al. 2017

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“…Discordance observed between cfDNA and tumour tissue may be due to the subclonal presentation of drivers in the tumour in later stages of the disease, which can affect the detectability of these drivers in cfDNA and impact concordance rates [86]. A multitude of studies across the field of solid tumours (i.e., prostate, NSCLC, breast, neuroblastoma, renal, gastrointestinal, pancreatic, thyroid and melanoma) focus on individual ( Table 2) or multiple malignancies (Table 3) and report a trend for high agreement between cfDNA and tumour tissue with respect to actionable driver alterations, but with notable exceptions [70,[89][90][91][92][93][94]. In Tables 2 and 3, we have included studies that compare the extent to which cfDNA reflects driver and actionable driver alterations of the primary or metastatic tumours.…”

Section: Gene Type and The Effect Of Drug Therapymentioning

confidence: 99%

Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Jahangiri

Hurst

2019

Cancers

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Somatic alterations to the genomes of solid tumours, which in some cases represent actionable drivers, provide diagnostic and prognostic insight into these complex diseases. Spatial and longitudinal tracking of somatic genomic alterations (SGAs) in patient tumours has emerged as a new avenue of investigation, not only as a disease monitoring strategy, but also to improve our understanding of heterogeneity and clonal evolution from diagnosis through disease progression. Furthermore, analysis of circulating-free DNA (cfDNA) in the so-called “liquid biopsy” has emerged as a non-invasive method to identify genomic information to inform targeted therapy and may also capture the heterogeneity of the primary and metastatic tumours. Considering the potential of cfDNA analysis as a translational laboratory tool in clinical practice, establishing the extent to which cfDNA represents the SGAs of tumours, particularly actionable driver alterations, becomes a matter of importance, warranting standardisation of methods and practices. Here, we assess the utilisation of cfDNA for molecular profiling of SGAs in tumour tissue across a broad range of solid tumours. Moreover, we examine the underlying factors contributing to discordance of detected SGAs between cfDNA and tumour tissue.

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“…In pancreatic cancer, high ctDNA levels of KRAS and/or other mutations have been associated with poor progression-free survival (PFS) and/or OS [47,48]. However, low concordance between the blood and tissue samples has been reported in patients with pancreatic ductal adenocarcinoma [49].…”

Section: Pancreatic and Biliary Tract Carcinomasmentioning

confidence: 99%

Circulating tumor DNA analysis in the era of precision oncology

et al. 2020

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The spatial and temporal genomic heterogeneity of various tumor types and advances in technology have stimulated the development of circulating tumor DNA (ctDNA) genotyping. ctDNA was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is associated with significant risk, when tumor tissue is insufficient or inaccessible, and/or when repeated assessment of tumor molecular abnormalities is needed to optimize treatment. The role of ctDNA is now well established in the clinical decision in certain alterations and tumors, such as the epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer and the v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer. The role of ctDNA analysis in other tumor types remains to be validated. Evolving data indicate the association of ctDNA level with tumor burden, and the usefulness of ctDNA analysis in assessing minimal residual disease, in understanding mechanisms of resistance to treatment, and in dynamically guiding therapy. ctDNA analysis is increasingly used to select therapy. Carefully designed clinical trials that use ctDNA analysis will increase the rate of patients who receive targeted therapy, will elucidate our understanding of evolution of tumor biology and will accelerate drug development and implementation of precision medicine. In this article we provide a critical overview of clinical trials and evolving data of ctDNA analysis in specific tumors and across tumor types.

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A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative

Cited by 57 publications

References 30 publications

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Circulating tumor DNA analysis in the era of precision oncology

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