Determination of RAS Mutation Status in Liquid Biopsies in Subjects With RAS Wild-type.PERSEIDA Study
Ontology highlight
ABSTRACT:
DISEASE(S): Ras Wild Type Mcrc
PROVIDER: 2216699 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, how well the tumour methylome can be monitored via liquid biopsies is relatively unknown. In this first of its kind study we made a direct comparison of two liquid biopsies: urine and blood, asking how well they represent the tumor methylome. Utilizing the Infinium Methylation EPIC BeadChip, we profiled DNA methylation in tissue, urine sediment and cell-free circulating DNA from four men with advanced stage prostate cancer. We show that both urine and plasma are viable surrogates for tumor tissue biopsies, capturing 78.63 and 62.21% of tumor-specific methylation alterations, respectively. We conclude that urine is an easily accessible and sensitive biofluid for the study of prostate cancer epigenomic alterations.
2020-04-22 | GSE119260 | GEO
Project description:Evaluating Liquid Biopsies for Methylomic Profiling of Prostate Cancer
| PRJNA488624 | ENA
Project description:Treatment options for patients with metastatic colorectal cancer (mCRC) are limited. This particularly affects the largest group of patients with RAS mutations, who are considered ineligible for therapy with antiEGFR antibodies. In this liquid biopsy-based study, we performed the first in-depth analysis of the RAS mutational status in initially RAS-mutated patients during first-line therapy. RAS status of twelve patients with initially RAS-mutated mCRC was monitored longitudinally in 69 liquid biopsy samples. We focused on patients with stable disease (SD) or partial remission (PR) during first-line therapy (11 patients). Detection of fragmented RAS-mutated circulating cell-free tumor DNA (ctDNA) in plasma was performed by digital-droplet PCR (ddPCR) and BEAMing. Patients' total tumor masses were determined by measuring the tumor volumes using CT scan data. All patients with PR or SD at first follow-up showed a significant decrease of RAS mutational load. In ten patients (91%), the ctDNA-based RAS mutational status converted to wild-type in ddPCR and BEAMing. Remarkably, conversions were observed early after the first cycle of chemotherapy. Plasma concentration of ctDNA was controlled by determination of methylated WIF1-promotor ctDNA burden as a second tumor marker for mCRC. Persistent presence of methylated WIF1-promotor fragments confirmed the ongoing release of ctDNA during treatment. In patients with initially RAS-mutated mCRC, RAS mutations rapidly disappeared during first-line therapy in liquid biopsy, independent of type and intensity of chemotherapy and irrespective of anti-VEGF treatments. Following our results demonstrating conversion of RAS-mutational status, potential effectiveness of anti-EGFR antibodies in selected patients becomes an attractive hypothesis for future studies.
| S-EPMC7378792 | biostudies-literature
Project description:INTRODUCTION. Liquid biopsies are a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. MATERIALS AND METHODS. TEPs from 297 subjects (53 EC patients, 40 patients with benign gynecologic conditions and 204 healthy women) were RNA-sequenced. DNA sequencing was performed in 519 primary tumor tissue samples and in16 plasma samples. Artificial intelligence was applied to sample classification. RESULTS. Platelet-dedicated classifier yielded AUC of 93.1% in test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was relatively low, with AUC of 60.7%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 91.4% and ctDNA blood samples with AUC of 87.5%. CONCLUSIONS Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work, involving more cases, is warranted.
2021-12-01 | GSE184904 | GEO
Project description:Mutation profiling in multiple myeloma using liquid biopsies
| PRJEB56136 | ENA
Project description:Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation. Therefore, liquid biopsy is an alternative or complementary method to tissue biopsy for the detection of some resistance mutations in EGFR arising during tyrosine kinase inhibitor treatment. Moreover, in some frail patients, or if the tumor lesion is not accessible to a tissue biopsy, a liquid biopsy can also detect some activating mutations in EGFR on initial assessment. Recent studies have evaluated the possibility of also using a liquid biopsy approach to detect an ALK rearrangement and/or the emergence during inhibitor treatment of some resistance mutations in ALK. These assessments can be performed by studying circulating tumor cells by fluorescent in situ hybridization and by immunocytochemistry and/or after the isolation of RNA from plasma samples, free or associated with platelets. Thus, the liquid biopsy may be a complementary or sometimes alternative method for the assessment of the ALK status in certain NSCLC patients, as well as a non-invasive approach for early detection of ALK mutations. In this review, we highlight the current data concerning the role of the liquid biopsy for the ALK status assessment for NSCLC patients, and we compare the different approaches for this evaluation from blood samples.
| S-EPMC5575609 | biostudies-literature
Project description:In study, liquid biopsy samples will be obtained from non-small cell lung cancer (NSCLC) including Squamous cell carcinoma, Adenocarcinoma and large cell carcinoma, colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC) patients who undergo treatment according to established standards of care (SoC) at the University Hospital Schleswig-Holstein (UKSH).
This study will observe the overall Variant Allele Frequency (VAF) of circulating tumour Desoxyribonucleic acid (ctDNA) levels over the patient therapeutic treatment course and will correlate these findings with tumour response as well as Kirsten rat sarcoma viral oncogene homolog (KRAS)mutation status.
| 6842 | ecrin-mdr-crc
Project description:Circulating Tumor Cells (CTCs) encompass multiple analytes, interrogated by sampling blood from patients with cancer. However, the clinical utility of tumor cell-based liquid biopsy has proven to be limited since CTCs are rare, and current technologies cannot process larger blood volumes required to isolate a sufficient number of tumor cells. We have described a high-throughput microfluidic prototype utilizing high-flow channels and amplification of cell sorting forces through magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from patients with metastatic cancer and achieving a median of 2,799 CTCs per patient. Isolation of many CTCs from individual patients enables characterization of their morphological and molecular heterogeneity, including cell and nuclear size and RNA expression. It also allows robust detection of gene copy number variation (CNV), a definitive cancer marker with potential diagnostic applications. High-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.
2024-08-27 | GSE255889 | GEO
Project description:Bacterial Heterochromatin Formation Through Liquid-Liquid Phase Separation
| PRJNA730564 | ENA
Project description:We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited. BEAMing ddPCR technology was employed to detect ctDNA RAS mutations, and logistic regression analyses were performed to investigate clinicopathological factors associated with discordance. The highest concordance ratios were observed in profiles with multiple metastatic sites when the liver was present (89.7%; 95% CI 84.8-93.2), profiles with synchronous disease without primary tumour resection (90.2%; 95% CI 83.6-94.3) and profiles with mCRC originating in the left colon (91.3%; 95% CI 85.0-95.0). Metachronous disease originating in the right colon (OR = 6.1; 95% CI 1.7-26.5; p-value = 0.006) or rectum (OR = 5.0; 95% CI 1.5-17.8; p-value = 0.009) showed the highest probability of discrepancies. Primary tumour resection and a higher frequency of single metastases in the peritoneum or lungs in these patients were associated with reduced plasmatic mutation allele fractions (MAFs) and an increased probability of showing false-negative genotypes. Additional testing of patients with mCRC originating in the right colon or rectum with a single non-mutated ctDNA test is advised before the choice of therapy.
| S-EPMC10377339 | biostudies-literature