Molecular Urine Test Identifies Lung Carcinoma Mutations
By LabMedica International staff writers Posted on 20 May 2015 |
The monitoring of circulating tumor DNA (ctDNA) is a promising technique that may provide clinicians with a faster, cheaper and less invasive way to evaluate the clinical status and response to therapy of cancer patients.
Disease progression in patients with metastatic non-small-cell lung cancer (NSCLC) is often heralded by the acquisition of epidermal growth factor receptor (EGFR) T790M resistance mutation following treatment with anti-EGFR inhibitors.
Scientists at Moores Cancer Center (La Jolla, CA, USA) took urine samples from patients with metastatic NSCLC who progressed on erlotinib treatment and ctDNA was extracted by a method that preferentially isolates short, fragmented ctDNA. Droplet digital polymerase chain reaction system (Bio-Rad; Hercules, CA, USA) was used to quantify the ctDNA and yielded an average of total amplifiable ctDNA per sample of 0.4 µg (range, 0.04 µg to 2.4 µg). Spiked cell lines were used for analytical characterization and demonstrated that the EGFR T790M assay had a lower limit of detection of two copies within a background of 60 ng of wild-type DNA, yielding an analytical sensitivity of 0.01%. EGFR status was analyzed using a PCR method that amplifies short target DNA fragments using kinetically-favorable binding conditions for a wild type blocking oligonucleotide, followed by massively parallel deep sequencing using a MiSeq desktop sequencer (Illumina; San Diego CA, USA).
EGFR T790M mutation in urine was detected in 15 of 22 (68%) of patients receiving anti-EGFR treatment until progression. Urine EGFR T790M mutation was detected in 10 out of 10 tissue-positive patients, giving 100% concordance. Urine ctDNA testing identified five additional patients who may be eligible for treatment with anti-T790M drugs, three of whom were tissue negative. The investigators showed that EGFR T790M mutation can be detected in urinary ctDNA up to three months before radiographic progression on first-line anti-EGFR tyrosine kinase inhibitor (TKI). When T790M positive patients were treated with third generation anti-EGFR TKIs, a decrease in ctDNA T790M load was observed as early as four hours after therapy on first day of treatment. The initial decrease in urinary T790M was followed by a spike in T790M during the first week of therapy.
Hatim Husain, MD, the lead author of the study and his colleagues concluded that this ctDNA assay for multiple genes via next-generation sequencing (NGS) might become a "liquid biopsy" that could serve as an alternative to invasive tissue biopsy. EGFR T790M mutation in urine was detected months before radiographic detection, and furthermore, urine ctDNA testing identified tissue negative patients who may be eligible for treatment with third generation anti-EGFR TKIs and monitoring of urinary T790M dynamics may predict clinical benefit or initial tumour burden. The study was presented at the EUROPEAN Lung Cancer Conference held April 15–18, 2015, in Geneva (Switzerland).
Related Links:
Moores Cancer Center
Bio-Rad
Illumina
Disease progression in patients with metastatic non-small-cell lung cancer (NSCLC) is often heralded by the acquisition of epidermal growth factor receptor (EGFR) T790M resistance mutation following treatment with anti-EGFR inhibitors.
Scientists at Moores Cancer Center (La Jolla, CA, USA) took urine samples from patients with metastatic NSCLC who progressed on erlotinib treatment and ctDNA was extracted by a method that preferentially isolates short, fragmented ctDNA. Droplet digital polymerase chain reaction system (Bio-Rad; Hercules, CA, USA) was used to quantify the ctDNA and yielded an average of total amplifiable ctDNA per sample of 0.4 µg (range, 0.04 µg to 2.4 µg). Spiked cell lines were used for analytical characterization and demonstrated that the EGFR T790M assay had a lower limit of detection of two copies within a background of 60 ng of wild-type DNA, yielding an analytical sensitivity of 0.01%. EGFR status was analyzed using a PCR method that amplifies short target DNA fragments using kinetically-favorable binding conditions for a wild type blocking oligonucleotide, followed by massively parallel deep sequencing using a MiSeq desktop sequencer (Illumina; San Diego CA, USA).
EGFR T790M mutation in urine was detected in 15 of 22 (68%) of patients receiving anti-EGFR treatment until progression. Urine EGFR T790M mutation was detected in 10 out of 10 tissue-positive patients, giving 100% concordance. Urine ctDNA testing identified five additional patients who may be eligible for treatment with anti-T790M drugs, three of whom were tissue negative. The investigators showed that EGFR T790M mutation can be detected in urinary ctDNA up to three months before radiographic progression on first-line anti-EGFR tyrosine kinase inhibitor (TKI). When T790M positive patients were treated with third generation anti-EGFR TKIs, a decrease in ctDNA T790M load was observed as early as four hours after therapy on first day of treatment. The initial decrease in urinary T790M was followed by a spike in T790M during the first week of therapy.
Hatim Husain, MD, the lead author of the study and his colleagues concluded that this ctDNA assay for multiple genes via next-generation sequencing (NGS) might become a "liquid biopsy" that could serve as an alternative to invasive tissue biopsy. EGFR T790M mutation in urine was detected months before radiographic detection, and furthermore, urine ctDNA testing identified tissue negative patients who may be eligible for treatment with third generation anti-EGFR TKIs and monitoring of urinary T790M dynamics may predict clinical benefit or initial tumour burden. The study was presented at the EUROPEAN Lung Cancer Conference held April 15–18, 2015, in Geneva (Switzerland).
Related Links:
Moores Cancer Center
Bio-Rad
Illumina
Read the full article by registering today, it's FREE!

Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
- Free digital version edition of LabMedica International sent by email on regular basis
- Free print version of LabMedica International magazine (available only outside USA and Canada).
- Free and unlimited access to back issues of LabMedica International in digital format
- Free LabMedica International Newsletter sent every week containing the latest news
- Free breaking news sent via email
- Free access to Events Calendar
- Free access to LinkXpress new product services
- REGISTRATION IS FREE AND EASY!

Sign in: Registered website members
Sign in: Registered magazine subscribers
Latest Pathology News
- AI Tool Accurately Determines Breast Cancer Prognosis
- Powerful New Tool Improves Tissue Cancer Analysis
- AI-Based Tool Measures Cancer Aggressiveness
- Novel Method Tracks Cancer Treatment in Cells Without Dyes or Labels
- New AI-Based Method Effectively Identifies Disease Phenotypes Using Light-Based Imaging
- AI Accurately Predicts Genetic Mutations from Routine Pathology Slides for Faster Cancer Care
- AI Tool Enhances Interpretation of Tissue Samples by Pathologists
- AI-Assisted Technique Tracks Cells Damaged from Injury, Aging and Disease
- Novel Fluorescent Probe Shows Potential in Precision Cancer Diagnostics and Fluorescence-Guided Surgery
- New Lab Model to Help Find Treatments for Aggressive Blood Cancer
- AI-Supported Microscopy Improves Detection of Intestinal Parasite Infections
- AI Performs Virtual Tissue Staining at Super-Resolution
- AI-Driven Preliminary Testing for Pancreatic Cancer Enhances Prognosis
- Cancer Chip Accurately Predicts Patient-Specific Chemotherapy Response
- Clinical AI Solution for Automatic Breast Cancer Grading Improves Diagnostic Accuracy
- Saliva-Based Testing to Enable Early Detection of Cancer, Heart Disease or Parkinson’s
Channels
Clinical Chemistry
view channel
Skin Swabs Could Detect Parkinson’s Years Before Symptoms Appear
Parkinson’s disease is notoriously difficult to diagnose in its early stages, as motor symptoms do not appear until later in the progression of the disease. The ability to detect the disease up to seven... Read more
New Clinical Chemistry Analyzer Designed to Meet Growing Demands of Modern Labs
A new clinical chemistry analyzer is designed to provide outstanding performance and maximum efficiency, without compromising affordability, to meet the growing demands of modern laboratories.... Read more
New Reference Measurement Procedure Standardizes Nucleic Acid Amplification Test Results
Nucleic acid amplification tests (NAATs) play a key role in diagnosing a wide range of infectious diseases. These tests are generally known for their high sensitivity and specificity, and they can be developed... Read moreMolecular Diagnostics
view channel
Highly Accurate Biomarkers Could Detect Ovarian Cancer Before Clinical Diagnosis
Ovarian cancer is a deadly and challenging disease, primarily because early detection is difficult. Most women (70-75%) are diagnosed only after the cancer has already spread, which significantly reduces... Read more
New Gene Tool to Enable Earlier Detection and Treatment of Cardiometabolic Diseases
Cardiometabolic diseases, which affect the heart, blood vessels, and the body's ability to process food and generate energy, are difficult to diagnose early due to the complex genetic changes that contribute... Read moreHematology
view channel
Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results
Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more
First Point-of-Care Heparin Monitoring Test Provides Results in Under 15 Minutes
Heparin dosing requires careful management to avoid both bleeding and clotting complications. In high-risk situations like extracorporeal membrane oxygenation (ECMO), mortality rates can reach about 50%,... Read moreImmunology
view channel
New AI System Uncovers Hidden Cell Subtypes to Advance Cancer Immunotherapy
To produce effective targeted therapies for cancer, scientists need to isolate the genetic and phenotypic characteristics of cancer cells, both within and across different tumors. These differences significantly... Read more
Evolutionary Clinical Trial to Identify Novel Biomarker-Driven Therapies for Metastatic Breast Cancer
Metastatic breast cancer, which occurs when cancer spreads from the breast to other parts of the body, is one of the most difficult cancers to treat. Nearly 90% of patients with metastatic cancer will... Read more
Groundbreaking Lateral Flow Test Quantifies Nucleosomes in Whole Venous Blood in Minutes
Diagnosing immune disruptions quickly and accurately is crucial in conditions such as sepsis, where timely intervention is critical for patient survival. Traditional testing methods can be slow, expensive,... Read moreMicrobiology
view channel
Early Detection of Gut Microbiota Metabolite Linked to Atherosclerosis Could Revolutionize Diagnosis
Cardiovascular disease is the leading cause of death worldwide, and atherosclerosis plays a critical role in its development. This chronic condition, characterized by the hardening and narrowing of arteries... Read more
Viral Load Tests Can Help Predict Mpox Severity
Mpox is a viral infection that causes flu-like symptoms and a characteristic rash, which evolves significantly over time and varies between patients. The disease spreads mainly through direct contact with... Read more
Gut Microbiota Analysis Enables Early and Non-Invasive Detection of Gestational Diabetes
Gestational diabetes mellitus is a common metabolic disorder marked by abnormal glucose metabolism during pregnancy, typically emerging in the mid to late stages. It significantly heightens the risk of... Read moreTechnology
view channel
Electronic Biosensors Used to Detect Pathogens Can Rapidly Detect Cancer Cells
A major challenge in healthcare is the early and affordable detection of serious diseases such as cancer. Early diagnosis remains difficult due to the complexity of identifying specific genetic markers... Read more
Safer, Portable and Low-Cost Imaging Solution to Revolutionize Biomedical Diagnostics
In diagnosing diseases and monitoring treatment, accurate and quick detection of temperature within biological tissues can be crucial, especially in early disease detection. Conventional methods such as... Read more
Multifunctional Nanomaterial Simultaneously Performs Cancer Diagnosis, Treatment, and Immune Activation
Cancer treatments, including surgery, radiation therapy, and chemotherapy, have significant limitations. These treatments not only target cancerous areas but also damage healthy tissues, causing side effects... Read moreIndustry
view channel
QuidelOrtho and BÜHLMANN Collaborate on Gastrointestinal Biomarker Tests
QuidelOrtho Corporation (San Diego, CA, USA) and BÜHLMANN Laboratories AG (Schönenbuch, Switzerland) have announced the availability of the BÜHLMANN fCAL turbo and fPELA turbo assays on QuidelOrtho's... Read more