Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs

Fabbri, Francesco; Carloni, Silvia; Zoli, Wainer; Ulivi, Paola; Gallerani, Giulia; Fici, Pietro; Chiadini, Elisa; Passardi, Alessandro; Frassineti, Giovanni Luca; Ragazzini, Angela; Amadori, Dino

doi:10.1016/j.canlet.2013.02.015

Cited by 204 publications

(165 citation statements)

References 31 publications

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“…Concerning this level of agreement found by our group and others 7,19,20 between CTCs and primary tumors, it has been hypothesized that the development of resistance to EGFR therapy is caused by rare cells with KRAS mutations that pre exist at low levels in mCRC with apparent KRAS wt. 22 Diaz et al 22 tested this hypothesis by analyzing 24 patients with mCRC, all of them with KRAS wt in primary tumor and resistant to anti-EGFR therapy.…”

Section: Discussionsupporting

confidence: 61%

“…Again, it can be explained by the cellular heterogeneity found in epithelial malignancies, which can be reflected by the heterogeneity found in CTCs. 7,19,22,23 Another explanation for our findings is the parallel progression model, which suggests that it may be possible to have various metastatic subclones which are disseminated early during disease development and remain dormant for years. 24 Additionally, we tried to correlate our findings with clinicalpathological characteristics of patients.…”

Section: Discussionmentioning

confidence: 90%

“…15 More recently, liquid biopsy technology, such as CTCs, have shown to be able to provide real time information about the tumor biology. Genotyping CTCs may be 19 using a dielectrophoresis-based device, had analyzed KRAS mutation (exon 2), and observed 50% of concordance between KRAS mutation in CTCs and matched primary tumor of mCRC. Mostert et al 7 found 5 of the 42 (12%) mCRC patients with KRAS mutation (codon 12/13) in CTCs by nested ASB-PCR.…”

Section: Discussionmentioning

confidence: 99%

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Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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Background: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. Objective: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Methods: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). Results: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P D 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Conclusion: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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“…Seit der Einführung des Imatinib zur Behandlung der chronisch myeloischen Leukämie hat sich in der Krebsmedizin ein Paradigmenwandel vollzogen, der inzwischen auch in der Onkologie der soliden Tumoren angekommen, deren molekulares Profil notorisch heterogen ist. Ihre Zellen sind einem ständigen Selektionsdruck unterworfen, der zu bisher nur in Ansät-zen verstandenen, aber für die Tumorbiologie kritischen molekulargenetischen und epigenetischen Veränderun-gen führt [28,29] [34].…”

Section: Introductionunclassified

“…Die Analyse der ctDNA besitzt damit ein wichtiges Potenzial für die frühere Identifikation von Therapieversagern, wie sie zum Beispiel während der Therapie des metastasierten kolorektalen Karzinoms mit anti-EGFR Antikörpern auftreten. In diesen Fällen werden im Verlauf in der ctDNA kras-Mutationen nachweisbar, die im Primärtumor zunächst nicht nachgewiesen wurden [29]. Das sekundäre Auftreten dieser Mutationen ist eher Ausdruck einer durch die molekularpathologische Primärdiag-nostik nicht erfassten Minoritätsfraktion von Tumorzellen, als dass diese unter dem Selektionsdruck der Therapie während des Progresses neu entstanden sind.…”

Section: Introductionunclassified

Zirkulierende Nukleinsäuren – ein neues Universum in der laboratoriumsmedizinischen Diagnostik

Neumaier

2016

LaboratoriumsMedizin

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Zusammenfassung: Zirkulierende zell-freie Nukleinsäu-ren (cfNA, meist als cfDNA bezeichnet) werden zunehmend als eine neue Klasse von diagnostischen Markern wahrgenommen. DNA, mRNA und miRNA zirkulieren weniger in "nackter Form", sondern sind verpackt und entgehen so einem schnellen Abbau im peripheren Blut. Abstract: Circulating cell-free nucleic acids (cfNA, mostly referred to as cfDNA) are increasingly being recognized as a promising new substrate for clinical laboratory diagnostics. DNA, mRNA and miRNA are less likely to circulate in the peripheral blood in a "free naked" form, but rather as a packaged form and thus are fairly protected from degradation. Together with the fact that both qualities and quantities of cfNA vary in a number of important human disorders, this may create an entirely new universe for laboratory diagnostics. First applications enter the arena of routine diagnostic health care, e.g. the sensitive and highly specific detection of tumor mutations that will allow for a molecular profiling of tumor relapse or therapy failure (the so-called "liquid biopsy"). Still, many open questions require resolution including their cross validation with established and important routine biomarkers in the health care lab. Furthermore, critical preanalytical questions, analytical validity and precision need to be addressed to secure the quality of the material analyzed and meaningful results, respectively. Last but not least, circulating nucleic acids uncover a whole new biology of signals traveling through our bodies under various conditions of health and disease. It will be of great scientific importance to understand their biochemical and pathobiochemical implications. It is significant for both the development and implementation of this new diagnostic field that clinical chemistry can provide the required expertise in all Unauthenticated Download Date | 5/11/18 12:36 AM

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Circulating tumor cell profiling for precision oncology

Labib

2021

Molecular Oncology

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Analysis of circulating tumor cells (CTCs) collected from patient's blood offers a broad range of opportunities in the field of precision oncology. With new advances in profiling technology, it is now possible to demonstrate an association between the molecular profiles of CTCs and tumor response to therapy. In this Review, we discuss mechanisms of tumor resistance to therapy and their link to phenotypic and genotypic properties of CTCs. We summarize key technologies used to isolate and analyze CTCs and discuss recent clinical studies that examined CTCs for genomic and proteomic predictors of responsiveness to therapy. We also point out current limitations that still hamper the implementation of CTCs into clinical practice. We finally reflect on how these shortcomings can be addressed with the likely contribution of multiparametric approaches and advanced data analytics.

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Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs

Cited by 204 publications

References 31 publications

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Zirkulierende Nukleinsäuren – ein neues Universum in der laboratoriumsmedizinischen Diagnostik

Circulating tumor cell profiling for precision oncology

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