Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR

Olmedillas‐López, Susana; Lévano-Linares, Dennis César; Alexandre, Carmen Laura Aúz; Vega-Clemente, Luz; Sánchez, E; Villagrasa, Alejandro; Ruíz-Tóvar, Jaime; García-Arranz, Mariano; Garcı́a-Olmo, Damián

doi:10.3748/wjg.v23.i39.7087

Cited by 11 publications

(6 citation statements)

References 51 publications

(62 reference statements)

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“…Although CEA has low sensitivity for monitoring CRC, and its benefit to overall survival remains under debate (Primrose et al, 2014), other proteins show some promise, such as epidermal growth factor-like domain 7 (EGFL7) (Hansen et al, 2017). In addition, body fluids other than blood (e.g., urine, saliva, pleural fluid, cerebrospinal fluid, and stool) show potential for monitoring tumor biomarkers (Olmedillas-Lopez et al, 2017; Siravegna et al, 2017a).…”

Section: Discussionmentioning

confidence: 99%

The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer

et al. 2019

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Background: Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate following disease recurrence. Treatment efficacy is maximized by providing tailored cancer treatment, ideally involving surgical resection and personalized neoadjuvant and adjuvant therapies, including chemotherapy, radiotherapy and increasingly, targeted therapy. Early detection of recurrence or disease progression results in more treatable disease and is essential to improving survival outcomes. Recent advances in the understanding of tumor genetics have resulted in the discovery of circulating tumor DNA (ctDNA). A growing body of evidence supports the use of these sensitive biomarkers in detecting residual disease and diagnosing recurrence as well as enabling targeted and tumor-specific adjuvant therapies. Methods: A literature search in Pubmed was performed to identify all original articles preceding April 2019 that utilize ctDNA for the purpose of monitoring response to colorectal cancer treatment. Results: Ninety-two clinical studies were included. These studies demonstrate that ctDNA is a reliable measure of tumor burden. Studies show the utility of ctDNA in assessing the adequacy of surgical tumor clearance and changes in ctDNA levels reflect response to systemic treatments. ctDNA can be used in the selection of targeted treatments. The reappearance or increase in ctDNA, as well as the emergence of new mutations, correlates with disease recurrence, progression, and resistance to therapy, with ctDNA measurement allowing more sensitive monitoring than currently used clinical tools. Conclusions: ctDNA shows enormous promise as a sensitive biomarker for monitoring response to many treatment modalities and for targeting therapy. Thus, it is emerging as a new way for guiding treatment decisions—initiating, altering, and ceasing treatments, or prompting investigation into the potential for residual disease. However, many potentially useful ctDNA markers are available and more work is needed to determine which are best suited for specific purposes and for improving specific outcomes.

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Section: Discussionmentioning

confidence: 99%

The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer

et al. 2019

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“…This work shows that Kras G12D was detected in OCs-1 when these cells were exposed without cell contact with CT26.WT cells in an enriched culture closer to liver microenvironment. Since the expected incorporation of Kras G12D in OC-1 cells was very low 7 , we decided to perform a ddPCR, which presents a higher sensitivity and accuracy of detection than other methods [39][40][41][42][43] . OCs-1 incorporated this oncogene in a stable way, while OCs-2 and OCs-3 were less susceptible.…”

Section: Discussionmentioning

confidence: 99%

Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice

Olivera

García‐Arranz

Sánchez

et al. 2022

Sci Rep

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Colorectal cancer cells can transfer the oncogene KRAS to distant cells, predisposing them to malignant transformation (Genometastasis Theory). This process could contribute to liver metastasis; besides, hepatic progenitor cells (HPCs) have been found to be involved in liver malignant neoplasms. The objective of this study is to determine if mouse HPCs—Oval cells (OCs)—are susceptible to incorporate Kras GAT (G12D) mutation from mouse colorectal cancer cell line CT26.WT and if OCs with the incorporated mutation behave like malignant cells. To achieve this, three lines of OCs in different conditions were exposed to CT26.WT cells through transwell co-culture for a week. The presence of KrasG12D and capacity to form tumors were analyzed in treated samples by droplet digital PCR and colony-forming assays, respectively. The results showed that the KrasG12D mutation was detected in hepatic culture conditions of undifferentiated OCs and these cells were capable of forming tumors in vitro. Therefore, OCs are susceptible to malignant transformation by horizontal transfer of DNA with KrasG12D mutation in an undifferentiated condition associated with the liver microenvironment. This study contributes to a new step in the understanding of the colorectal metastatic process.

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“…Similar to our present results, codon 12 mutations were the most common KRAS mutations found in our previous study on Iranian samples, although other KRAS mutations at codons 12, 13, 20, 63, 117, 146 and 43 were also found previously[ 13 ]. Additionally, a recent study demonstrated the detection of KRAS G12D mutation in stool samples from patients with colorectal carcinoma by using droplet PCR[ 17 ]. Clinical data available from those patients for who KRAS testing in tumor tissue was carried out correlated to KRAS mutation status in stool.…”

Section: Discussionmentioning

confidence: 99%

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

Youssef

Sarhadi

Ehsan

et al. 2017

WJG

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AIMTo study cancer hotspot mutations by next-generation sequencing (NGS) in stool DNA from patients with different gastrointestinal tract (GIT) neoplasms.METHODSStool samples were collected from 87 Finnish patients diagnosed with various gastric and colorectal neoplasms, including benign tumors, and from 14 healthy controls. DNA was isolated from stools by using the PSP® Spin Stool DNA Plus Kit. For each sample, 20 ng of DNA was used to construct sequencing libraries using the Ion AmpliSeq Cancer Hotspot Panel v2 or Ion AmpliSeq Colon and Lung Cancer panel v2. Sequencing was performed on Ion PGM. Torrent Suite Software v.5.2.2 was used for variant calling and data analysis.RESULTSNGS was successful in assaying 72 GIT samples and 13 healthy controls, with success rates of the assay being 78% for stomach neoplasia and 87% for colorectal tumors. In stool specimens from patients with gastric neoplasia, five hotspot mutations were found in APC, CDKN2A and EGFR genes, in addition to seven novel mutations. From colorectal patients, 20 mutations were detected in AKT1, APC, ERBB2, FBXW7, KIT, KRAS, NRAS, SMARCB1, SMO, STK11 and TP53. Healthy controls did not exhibit any hotspot mutations, except for two novel ones. APC and TP53 were the most frequently mutated genes in colorectal neoplasms, with five mutations, followed by KRAS with two mutations. APC was the most commonly mutated gene in stools of patients with premalignant/benign GIT lesions.CONCLUSIONOur results show that in addition to colorectal neoplasms, mutations can also be assayed from stool specimens of patients with gastric neoplasms.

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Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR

Cited by 11 publications

References 51 publications

The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer

The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer

Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

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