Blood circulating tumor DNA for non‐invasive genotyping of colon cancer patients

Siravegna, Giulia; Bardelli, Alberto

doi:10.1016/j.molonc.2015.12.005

Cited by 57 publications

(44 citation statements)

References 43 publications

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“…Strickler and colleagues recently reported cell-free DNA genomic profiling results for over 1,000 colorectal carcinoma patients, but analysis was largely focused on short variant alterations, and no comparison with paired tissue samples was available (22). Alternative applications for ctDNA, including detection of residual disease and early recurrence, rather than identification of actionable GAs, have been the focus of other studies and are not formally examined in our analysis (35, 36). Despite the promise of ctDNA, there are clear disadvantages in relying solely on ctDNA testing, including lack of sufficient ctDNA in approximately 18% of samples, low purity (MSAF) of ctDNA, which can lead to diminished ability to reliably detect gene amplifications, and overall smaller gene panels with ctDNA versus tissue, which limit the total number of assessable alterations.…”

Section: Discussionmentioning

confidence: 99%

Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

Schrock

Pavlick

Klempner

et al. 2018

Clinical Cancer Research

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Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative. Experimental Design: Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples. Results: Evidence of ctDNA was detected in 344of417 samples (82%), and of these, ≥1 reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented. Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with gastrointestinal carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced gastrointestinal cancers as a complementary approach to tissue testing, and further investigation is warranted.

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Section: Discussionmentioning

confidence: 99%

Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

Schrock

Pavlick

Klempner

et al. 2018

Clinical Cancer Research

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“…Similarly, most cancers shed cell-free circulating tumor DNA (ctDNA) in the blood[30]. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies.…”

Section: Liquid Biopsies: Circulating Tumor Cells and Circulating Tummentioning

confidence: 99%

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

Veen

Søreide

2017

WJGO

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In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from “what is taken out” (e.g., how much liver has to be resected) to “what is left behind” (that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.

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“…It has also been reported that liquid biopsies can be used for KRAS mutation analysis in colon cancer and BRAF mutation analysis in melanoma (72,73).…”

Section: Key To Success In Molecular Processes: Communicationmentioning

confidence: 99%

“…Obtaining genetic material from both the primary tumor and metastatic deposits at the same time may be of benefit in our understanding of tumor heterogeneity (123). At this stage, sequential administration of CTC analyzes before, during, and after treatment can provide information about tumor progression and possible resistance mechanisms (73,124,125). …”

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confidence: 99%

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

Uzun

Sarıoğlu²

2017

TJPATH

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Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities.This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs) and cell-free circulating nucleic acids), effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned.Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.Key Words: Molecular Pathology, Tissue saving, Tumor enrichment, Tumor percentage INTRODUCTION "Molecular Pathology" is one of the pathological methods with expanding role in patient diagnosis, prediction of prognosis and treatment. Tissue and cellular material from patients have always been valued in pathology laboratories; however they gain additional importance in the molecular pathology era with the increase in new disease classifications according to molecular changes and new targeted therapy options being determined with predictive molecular testing.While the value of diseased and normal tissue is expanding with the advances in immunohistochemistry and molecular pathology, minimally invasive techniques have taken the place of radical processes in tissue sampling along with developments in the technology. These techniques are better for the comfort of the patient but they also have disadvantages, as they provide smaller amounts of tissue for diagnosis. The management of tissues obtained with these techniques can be problematic for pathologists. The application of individualized treatment regimens developed in recent years has depended on molecular studies. The adequacy of the obtained material and its reliability for molecular investigation are of utmost importance in many cases.The diagnosis of lung carcinomas is usually made with small biopsies or cytological materials and these materials are generally the only options for further studies. Transthoracic, transbronchial fine needle aspirations, forceps biopsies, bronchial brushes, and washes are some of these materials (1). A molecular examination requires the best process and good sample quality. The most important factor for the success of molecular tests is the number of tumor cells and the percentage of mutant cells (2). The requirements for tumor cell number and mutation perc...

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Blood circulating tumor DNA for non‐invasive genotyping of colon cancer patients

Cited by 57 publications

References 43 publications

Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

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