SENTIS Cancer & Discovery ctDNA Test at Chughtai Lab

Introduction to SENTIS Cancer & Discovery Test (Ct DNA) at Chughtai Lab

The SENTIS Cancer & Discovery Test (Ct DNA) is a state-of-the-art liquid biopsy designed to detect and analyze circulating tumor DNA (ctDNA) in the bloodstream. Developed using advanced Next-Generation Sequencing (NGS) technology, this molecular diagnostic test offers a non-invasive method to profile the genetic landscape of solid tumors. As cancer cells grow and undergo natural processes like apoptosis or necrosis, they shed tiny fragments of their genetic material into the circulatory system. These fragments, known as circulating tumor DNA, carry the exact somatic mutations, insertions, deletions, and gene fusions that drive the patient’s specific malignancy.

By analyzing these blood-borne genetic markers, the SENTIS Cancer & Discovery Test provides oncologists with critical genomic insights without the need for invasive surgical tissue biopsies. This is particularly valuable when a tumor is anatomically inaccessible, when a patient is unfit for surgery, or when previous tissue samples are insufficient for molecular analysis. The clinical utility of this test spans across multiple stages of cancer care, including identifying targetable therapeutic mutations, monitoring treatment response, detecting minimal residual disease (MRD), and identifying emerging resistance mutations before they manifest clinically or radiologically.

At Chughtai Lab, this highly sophisticated molecular test is performed using cutting-edge genomic platforms and analyzed via robust bioinformatics pipelines. By mapping the unique genetic profile of a patient’s tumor, the SENTIS test empowers clinical oncologists to design highly personalized, targeted treatment strategies, shifting the paradigm of cancer care from a one-size-fits-all approach to precise, evidence-based medicine.

Clinical Procedure: What to Expect

Patient Preparation

Because the SENTIS Cancer & Discovery Test is a highly sensitive molecular assay analyzing cell-free DNA, proper patient preparation is essential to ensure sample integrity and accurate genetic sequencing. Patients should observe the following guidelines:

• No Strict Fasting Required: Fasting is generally not mandatory for this test. However, patients are advised to avoid excessively fatty meals immediately before the blood draw to prevent lipemia, which can interfere with optical sequencing instruments.
• Hydration: It is highly recommended to drink plenty of water prior to the procedure. Good hydration expands blood volume and makes venipuncture easier and more efficient.
• Timing Relative to Therapies: The timing of the blood draw should be carefully coordinated with the treating oncologist. Ideally, the sample should be collected before initiating a new line of cancer therapy, or when there is clinical suspicion of disease progression or treatment resistance.
• Recent Medical Interventions: Inform the laboratory staff if you have recently undergone major surgery, radiotherapy, or experienced severe physical trauma. These events can temporarily elevate the levels of normal, non-tumor cell-free DNA (cfDNA) in the bloodstream, which may dilute the circulating tumor DNA and affect the test’s sensitivity.
• Documentation: Patients must provide a complete clinical history, including the primary cancer diagnosis, current stage, details of ongoing or past therapies (such as chemotherapy, immunotherapy, or targeted therapy), and any previous tissue biopsy reports.

During the Procedure

The collection process for the SENTIS Cancer & Discovery Test is straightforward, minimally invasive, and resembles a standard blood draw, though it requires specialized handling:

• Venipuncture: A trained phlebotomist at Chughtai Lab will locate a suitable vein, typically in the arm, and sanitize the area with an antiseptic solution.
• Specialized Collection Tubes: Unlike routine blood tests, the SENTIS test requires specialized cell-stabilizing tubes (such as Streck tubes). These tubes contain preservatives that prevent healthy white blood cells from lysing (breaking open) after collection. If normal white blood cells rupture, they release genomic DNA into the plasma, diluting the tumor DNA and compromising the test’s accuracy.
• Sample Volume: Approximately 10 to 20 mL of blood (usually filled across two specialized tubes) is collected to ensure an adequate concentration of cell-free DNA is obtained for sequencing.
• Duration and Sensation: The entire blood collection process takes approximately 5 to 10 minutes. Patients will feel a brief, mild pinch as the needle is inserted, but the procedure is otherwise painless.
• Post-Collection Handling: Immediately after collection, the tubes are gently inverted to mix the blood with the preservative. The samples are then carefully logged, packaged, and transported under strict temperature-controlled conditions to the molecular pathology department for plasma separation and DNA extraction.

When is a SENTIS Cancer & Discovery Test Performed?

Advanced Solid Tumor Profiling

The primary clinical indication for the SENTIS Cancer & Discovery Test is the comprehensive genomic profiling of advanced or metastatic solid tumors. When a patient is diagnosed with advanced stage III or IV cancers—such as non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer, or ovarian cancer—identifying the specific genetic drivers of the tumor is essential. This liquid biopsy allows oncologists to screen for actionable mutations across dozens of genes simultaneously, guiding the selection of FDA-approved targeted therapies.

Inaccessible Tumors or Insufficient Tissue Samples

In many clinical scenarios, performing a traditional surgical biopsy or core needle biopsy is highly challenging or medically contraindicated. This occurs when tumors are located near vital organs, deep within the lung parenchyma, or inside the central nervous system. Additionally, even when a tissue biopsy is performed, the sample obtained may be insufficient (Quantity Not Sufficient, or QNS) for extensive molecular testing. In these cases, the SENTIS liquid biopsy serves as an invaluable, non-invasive alternative to obtain the necessary genetic data.

Monitoring Treatment Response and Detecting Minimal Residual Disease

Following primary interventions such as surgical resection, chemotherapy, or radiotherapy, physicians utilize the SENTIS test to monitor the presence of residual cancer cells. The persistence of ctDNA in the blood after curative-intent therapy, known as Minimal Residual Disease (MRD), is a strong predictor of cancer recurrence. By tracking ctDNA levels over time, oncologists can objectively assess whether a treatment is successfully eradicating the tumor or if early recurrence is occurring, long before it becomes visible on standard CT, MRI, or PET scans.

Identifying Acquired Resistance Mutations

While targeted therapies (such as tyrosine kinase inhibitors) are highly effective, tumors often adapt over time by developing secondary genetic mutations that render the treatment ineffective. When a patient who was previously stable begins to show signs of clinical progression, the SENTIS test is performed to identify these acquired resistance mutations. Detecting these mutations (such as the EGFR T790M or C797S mutations in lung cancer) allows clinicians to promptly switch the patient to next-generation targeted drugs designed to bypass these specific resistance mechanisms.

Assessing Tumor Heterogeneity

Solid tumors are highly heterogeneous, meaning different parts of the primary tumor and various metastatic lesions may harbor different genetic mutations. A traditional tissue biopsy only captures genetic information from the single site that was sampled, potentially missing critical mutations present elsewhere in the body. Because ctDNA is shed from all active tumor sites into the systemic circulation, the SENTIS Cancer & Discovery Test provides a comprehensive, global representation of the patient’s entire tumor burden and its diverse genetic alterations.

What Does a SENTIS Cancer & Discovery Test Detect?

The SENTIS Cancer & Discovery Test utilizes high-depth Next-Generation Sequencing to detect a wide array of somatic genetic alterations, including single nucleotide variants (SNVs), small insertions and deletions (indels), copy number variations (CNVs), and genomic rearrangements/fusions. Specifically, the test is designed to detect:

• EGFR Mutations: Common sensitizing mutations (such as Exon 19 deletions and L858R point mutations) as well as resistance mutations (T790M and C797S) in non-small cell lung cancer.
• KRAS Mutations: Activating mutations in codons 12, 13, 61, and 146, which are critical for determining therapy selection in colorectal, lung, and pancreatic cancers.
• NRAS Mutations: Key genetic variants in colorectal cancer and melanoma that influence response to anti-EGFR therapies.
• BRAF Mutations: Specifically the V600E and V600K mutations, which are targetable in melanoma, colorectal cancer, and non-small cell lung cancer.
• PIK3CA Mutations: Alterations in the PI3K/AKT/mTOR pathway, commonly found in breast, endometrial, and ovarian malignancies.
• ERBB2 (HER2) Amplifications and Mutations: Copy number gains and activating mutations relevant in breast, gastric, and lung cancers.
• ALK Gene Fusions: Chromosomal rearrangements (such as EML4-ALK) that indicate sensitivity to ALK inhibitors in lung cancer.
• ROS1 and RET Fusions: Targetable oncogenic fusions found in subset populations of non-small cell lung cancers and thyroid cancers.
• MET Alterations: Including MET Exon 14 skipping mutations and MET gene amplifications associated with primary driving oncogenesis and acquired resistance.
• BRCA1 and BRCA2 Mutations: Somatic alterations that guide the use of PARP inhibitors in ovarian, breast, prostate, and pancreatic cancers.
• ESR1 Mutations: Genetic changes in the estrogen receptor gene that emerge during endocrine therapy in breast cancer, indicating resistance to standard aromatase inhibitors.
• KIT and PDGFRA Mutations: Primary driving mutations in gastrointestinal stromal tumors (GIST).
• NTRK1, NTRK2, and NTRK3 Fusions: Highly actionable, tumor-agnostic fusions that respond exceptionally well to TRK inhibitors.
• Tumor Mutational Burden (TMB): An estimation of the number of mutations per megabase of DNA, serving as a predictive biomarker for response to immune checkpoint inhibitors.
• Microsatellite Instability (MSI): Detection of mismatch repair deficiency from blood, indicating eligibility for immunotherapy.
• TP53 Mutations: Alterations in the tumor suppressor gene TP53, providing prognostic value across almost all solid tumor types.

Turnaround Time and Report Access at Chughtai Lab

Due to the highly complex nature of Next-Generation Sequencing, which involves DNA extraction, library preparation, high-throughput sequencing, and intensive bioinformatics analysis by specialized genomic scientists, the turnaround time for the SENTIS Cancer & Discovery Test is typically 14 to 21 business days. Each sample undergoes rigorous quality control checks at every stage to ensure maximum analytical sensitivity and specificity.

Once the genomic analysis is complete, the comprehensive molecular report is compiled and verified by consultant pathologists and molecular geneticists. Chughtai Lab provides convenient digital access to these reports. Patients and their treating oncologists can view and download the detailed PDF report directly from the official Chughtai Lab website or through the Chughtai Lab mobile application. Physical copies of the report can also be collected from any major Chughtai Lab diagnostic center across Pakistan, including primary hubs in Lahore, Karachi, Islamabad, and Peshawar.

SENTIS Findings Overview

The following table outlines the key genetic parameters evaluated during the SENTIS Cancer & Discovery Test, along with their clinical implications:

Structure / Parameter Evaluated	Normal Findings	Possible Abnormal Findings
EGFR Gene Status	Wild-type (No oncogenic mutations detected)	Exon 19 deletions, L858R mutation (sensitizing); T790M, C797S mutations (resistance)
KRAS / NRAS Pathway	No mutations detected in codons 12, 13, 61, or 146	Activating mutations (e.g., KRAS G12D, G12C, G12V), indicating resistance to anti-EGFR therapies
BRAF Gene Status	Wild-type (No mutations detected)	BRAF V600E or V600K mutations, indicating eligibility for combined BRAF/MEK inhibitor therapy
ALK / ROS1 / RET Status	No chromosomal rearrangements or fusions detected	Oncogenic fusions (e.g., EML4-ALK), indicating high sensitivity to specific tyrosine kinase inhibitors
BRCA1 / BRCA2 Status	No somatic pathogenic variants detected	Pathogenic mutations, suggesting potential benefit from PARP inhibitor therapies
ESR1 Mutation Status	Wild-type (No mutations detected)	Ligand-binding domain mutations (e.g., D538G, Y537S), indicating resistance to standard aromatase inhibitors
Blood Tumor Mutational Burden (bTMB)	Low TMB (Few somatic mutations per megabase)	High bTMB, which may correlate with a favorable response to cancer immunotherapies
ctDNA Fraction (Tumor Fraction)	Undetectable or 0% ctDNA in cell-free DNA	Elevated ctDNA fraction, reflecting active tumor burden, disease progression, or minimal residual disease

Note: Diagnostic findings should always be interpreted by a qualified healthcare professional together with the patient’s symptoms, medical history, physical examination, laboratory investigations, previous imaging studies, and other relevant clinical information. Additional investigations or specialist consultation may be recommended depending on the findings.

Why Choose Chughtai Lab for SENTIS Cancer & Discovery Test?

• Advanced Molecular Pathology: Chughtai Lab houses a state-of-the-art molecular diagnostics division equipped with modern Next-Generation Sequencing (NGS) platforms.
• Expert Pathologists and Geneticists: Reports are analyzed and signed off by highly qualified consultant pathologists and molecular geneticists with specialized training in oncology diagnostics.
• Nationwide Network: With presence in major cities across Pakistan, patients can easily access specialized sample collection facilities.
• Strict Quality Control: The laboratory adheres to international quality standards, ensuring highly accurate, reproducible, and reliable genomic sequencing results.
• Specialized Sample Handling: Chughtai Lab utilizes specialized cell-stabilizing collection tubes and maintains strict cold-chain logistics to preserve delicate cell-free DNA.
• Digital Report Access: Patients and oncologists can instantly access comprehensive molecular reports via the Chughtai Lab website and mobile app.
• Home Sample Collection: For advanced cancer patients who may find it difficult to travel, Chughtai Lab offers professional home sample collection services by trained phlebotomists.
• Comprehensive Clinical Support: Chughtai Lab provides detailed, clinically actionable reports that list potential targeted therapies and clinical trials aligned with the detected genetic alterations.