KRAS and BRAF mutations in serum exosomes from patients with colorectal cancer in a Chinese population

Hao, Yilong; Li, Yong‐Mei; Ye, Ming; Guo, Yanyan; Li, Qiuwen; Peng, Xiumei; Wang, Qi; Zhang, Shu‐Fang; Zhao, Huixia; Zhang, He; Li, Guanghui; Zhu, Jianhua; Wu, Xiao

doi:10.3892/ol.2017.5889

Cited by 44 publications

(29 citation statements)

References 56 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Table 3). While PA protocol isolates more mutant copies than CF, its diagnostic sensitivity was still low compared to previous studies (56% 30,31 ). Two reasons may explain this performance: (A) the use of 500 µl of plasma instead of 1-2 ml of more as previously reported 31 ; (B) the mutant cohort included patients undergoing 1-3 months of BRAFi treatment as shown in Supplementary Table 3.…”

Section: Discussionmentioning

confidence: 90%

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients

Zocco¹,

Bernardi

Novelli

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Detection of BRAFV600E within cell free tumor DNA (ctDNA) is emerging as a promising means to improve patients’ stratification or enable BRAF inhibitor (BRAFi) therapeutic monitoring in a minimally invasive manner. Here, we investigated whether extracellular vesicle-(EV)-associated-DNA (EV-DNA) has value as an alternative source of circulating BRAFV600E. To do so, we identified a clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy. This protocol uses a peptide with high affinity for EVs and it has been found to recover more mutant DNA from plasma than standard ultracentrifugation. Molecular analyses revealed that mutant DNA is largely unprotected from nuclease digestion, interacting with the outer side of the EV membrane or directly with the peptide. When used on clinical samples, we found that the protocol improves the detection of BRAFV600E gene copies in comparison to the reference protocol for ctDNA isolation. Taken together, these findings indicate that EVs are a promising source of mutant DNA and should be considered for the development of next-generation liquid biopsy approaches.

show abstract

Section: Discussionmentioning

confidence: 90%

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients

Zocco¹,

Bernardi

Novelli

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In CRC, genomic DNA extracted from the tumor tissues of 35 patients with histologically confirmed CRC and exosomal mRNA obtained from peripheral blood of the corresponding patients prior to surgery are studied together. 87 The KRAS mutation rates in tumor tissues and the matched serum exosomes were 57.6% and 42.4%, respectively; BRAF mutation was 24.2% and 18.2%, respectively. There was no significant difference between the rate detected by tissue and serum exosomes.…”

Section: Introductionmentioning

confidence: 90%

Biomarkers for early diagnosis, prognosis, prediction, and recurrence monitoring of non-small cell lung cancer

Tang¹,

Qiao²,

Xu³

et al. 2017

OTT

View full text Add to dashboard Cite

Despite advances in the management of non-small cell lung cancer, it remains to be the leading cause of cancer-related deaths worldwide primarily because of diagnosis at a late stage with an overall 5-year survival rate of 17%. A reduction in mortality was achieved by low-dose computed tomography screening of high-risk patients. However, the benefit was later challenged by the high false positive rate, resulting in unnecessary follow-ups, thus entailing a burden on both the health care system and the individual. The diagnostic dilemma imposed by imaging modalities has created a need for the development of biomarkers capable of differentiating benign nodules from malignant ones. In the past decade, with the advancements in high-throughput profiling technologies, a huge amount of work has been done to derive biomarkers to supplement clinical diagnosis. However, only a few of them have efficient sensitivity and specificity to be utilized in clinical settings. Therefore, there is an urgent need for the development of sensitive and specific means to detect and diagnose lung cancers at an early stage, when curative interventions are still possible. Due to the invasiveness of tissue biopsies and inability to capture tumor heterogeneity, nowadays enormous efforts have been invested in the development of technologies and biomarkers that enable sensitive and cost-effective testing using substrates that can be obtained in a noninvasive manner. This review, primarily focusing on liquid biopsy, summarizes all documented potential biomarkers for diagnosis, monitoring recurrence treatment response.

show abstract

“…Finally, Hao et al assayed the KRAS/BRAF mutational status of serum Exo from metastatic CRC patients, and found a high concordance with primary tumors (79). Further studies are nevertheless needed before considering this approach as a reliable alternative to molecular testing on tissue biopsy since these results may have been biased by serum sample preparation or Exo collection, as well as by methods applied for DNA extraction or sequencing.…”

Section: Predicting Primary Resistancementioning

confidence: 99%

Liquid Biopsy as a Tool Exploring in Real-Time Both Genomic Perturbation and Resistance to EGFR Antagonists in Colorectal Cancer

et al. 2020

View full text Add to dashboard Cite

The treatment of metastatic colorectal cancer (mCRC) has improved since the introduction of the epithelial growth factor receptor (EGFR) inhibitors as cetuximab and panitumumab. However, only patients with peculiar genomic profiles benefit from these targeting therapies. In fact, the molecular integrity of RAS genes is a predominant factor conditioning both primary and acquired resistance in non-responders although additional molecular derangements induced by selective anti-EGFR pressure may concur to the failure of those disease treatment, liquid biopsy (LB) appears as a surrogate of tissue biopsy, provides the genomic information to reveal tumor resistance to anti-EGFR agents, the detection of minimal residual disease before adjuvant therapies, and the discovery of tumor molecular status suitable for rechallenging treatments with EGFR antagonists. LB investigates circulating tumor cells (CTCs), cellfree tumor DNA (ctDNA), and tumor-derived exosomes. In mCRC, ctDNA analysis has been demonstrated as a useful method in the mutational tracking of defined genes as well as on tumor burden and detection of molecular alterations driving the resistance to anti-EGFR targeting treatments. However, despite their efficiency in molecular diagnosis and prognostic evaluation of mCRC, the affordability of these procedures is prevalently restricted to research centers, and the lack of consensus validation prevents their translation to clinical practice. Here, we revisit the major mechanisms responsible for resistance to EGFR blockade and review the different methods of LB potentially useful for treatment options in mCRC.

show abstract

KRAS and BRAF mutations in serum exosomes from patients with colorectal cancer in a Chinese population

Cited by 44 publications

References 56 publications

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients

Biomarkers for early diagnosis, prognosis, prediction, and recurrence monitoring of non-small cell lung cancer

Liquid Biopsy as a Tool Exploring in Real-Time Both Genomic Perturbation and Resistance to EGFR Antagonists in Colorectal Cancer

Contact Info

Product

Resources

About