Foundation Medicine CDx Test at Chughtai Lab

Foundation Medicine CDx at Chughtai Lab

Foundation Medicine CDx, specifically known as FoundationOne CDx, is a pioneering next-generation sequencing (NGS) based in vitro diagnostic device designed to revolutionize cancer care through precision oncology. This advanced molecular test is FDA-approved for all solid tumors, offering comprehensive genomic profiling (CGP) that analyzes 324 genes known to drive cancer growth. By utilizing state-of-the-art hybridization-capture technology, the test detects substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in these genes, as well as select gene rearrangements. Furthermore, it evaluates critical genomic signatures such as Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI), which are essential biomarkers for determining eligibility for modern immunotherapies. Chughtai Lab, Pakistan’s premier diagnostic network, facilitates access to this world-class genomic profiling test, enabling oncologists across the country to make highly informed, personalized treatment decisions for their patients.

The clinical importance of Foundation Medicine CDx lies in its role as a companion diagnostic. Rather than relying on a one-size-fits-all treatment model, this test identifies specific molecular alterations within a patient’s tumor that match with FDA-approved targeted therapies. This targeted approach maximizes therapeutic efficacy while minimizing unnecessary side effects from ineffective treatments. For patients with advanced, metastatic, or refractory cancers, the test provides a comprehensive molecular blueprint of the disease, uncovering therapeutic avenues that traditional diagnostic methods, such as single-gene PCR or immunohistochemistry (IHC), might miss. By analyzing a broad panel of genes simultaneously, Foundation Medicine CDx conserves precious tumor tissue samples and saves critical time, which is of paramount importance in clinical oncology management.

Clinical Procedure: What to Expect

Patient Preparation

Because Foundation Medicine CDx is performed on tumor tissue previously obtained during a biopsy or surgical resection, there is no direct physical preparation required from the patient. No fasting, dietary restrictions, or medication adjustments are necessary for this test. However, the preparation process involves critical pathological and administrative coordination, which is managed efficiently by Chughtai Lab:

• Tissue Block Retrieval: The patient or their clinical team must provide the formalin-fixed paraffin-embedded (FFPE) tumor tissue block. This block is typically stored in the pathology department of the hospital where the initial biopsy or surgery was performed.
• Pathology Review: Chughtai Lab’s expert histopathologists will review the tissue block to ensure it meets the strict quality and quantity criteria required by Foundation Medicine. The sample must contain a minimum tumor cell content (optimally 30% or more, with a absolute minimum of 20%) and sufficient tissue volume to ensure successful DNA and RNA extraction.
• Alternative Slide Preparation: If the physical tissue block cannot be sent, Chughtai Lab can assist in preparing the required number of unstained slides (typically 10 to 15 slides cut at 4-5 microns thickness) along with one hematoxylin and eosin (H&E) stained slide, conforming to international shipping and testing standards.
• Clinical Documentation: Patients must provide a completed consent form, a detailed clinical history, and the oncologist’s prescription to ensure accurate clinical correlation.

During the Procedure

The procedure for Foundation Medicine CDx is entirely laboratory-based and does not involve any direct physical discomfort for the patient. Once the appropriate tumor tissue sample is received and verified at Chughtai Lab, the specialized molecular diagnostics team initiates the international shipping protocol. The tissue specimen is securely packaged in temperature-controlled, specialized transport kits to maintain sample integrity during transit to the designated Foundation Medicine testing facility.

Upon arrival at the testing laboratory, highly automated, state-of-the-art next-generation sequencing (NGS) workflows are initiated. The process begins with the extraction of genomic DNA and RNA from the FFPE tumor sections. The extracted nucleic acids undergo hybridization capture to isolate the coding regions of the 324 cancer-related genes. These regions are then sequenced to high depth using advanced high-throughput sequencing platforms. Sophisticated bioinformatic pipelines analyze the sequencing data, comparing it against extensive clinical databases to identify pathogenic alterations and calculate genomic signatures like TMB and MSI. The entire process, from sample receipt at Chughtai Lab to the delivery of the final comprehensive clinical report, is closely monitored to ensure the highest standards of quality, safety, and clinical accuracy.

When is a Foundation Medicine CDx Test Performed?

Advanced or Metastatic Solid Tumors

Physicians frequently request the Foundation Medicine CDx test when a patient is diagnosed with advanced, stage IV, or metastatic solid tumors. In these advanced stages, identifying the precise molecular drivers of the cancer is critical, as standard systemic chemotherapy may offer limited benefits. By identifying specific genomic alterations, the test allows oncologists to select highly effective targeted therapies as first-line or subsequent-line treatments, significantly improving progression-free survival and overall patient outcomes.

Identification of Companion Diagnostic Indications

This test is performed when an oncologist needs to determine if a patient qualifies for specific FDA-approved targeted therapies. For instance, in non-small cell lung cancer (NSCLC), the test identifies EGFR mutations, ALK fusions, or ROS1 rearrangements, which directly match patients with specific tyrosine kinase inhibitors (TKIs). In ovarian and prostate cancers, the detection of BRCA1/2 mutations or other homologous recombination repair (HRR) gene alterations guides the use of PARP inhibitors, ensuring that patients receive therapies tailored to their tumor’s genetic profile.

Evaluation of Immunotherapy Eligibility

Immunotherapy has emerged as a highly effective treatment modality for various cancers, but its efficacy depends heavily on specific biomarkers. The Foundation Medicine CDx test is performed to evaluate Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status across all solid tumors. A high TMB (typically defined as 10 or more mutations per megabase) or an MSI-High status indicates that the tumor is highly immunogenic, making the patient an excellent candidate for immune checkpoint inhibitors, such as pembrolizumab, regardless of the tumor’s anatomical origin.

Refractory Cancers with Limited Standard Options

When a patient’s cancer has progressed despite undergoing standard-of-care chemotherapy and radiotherapy, clinical options become limited. In such refractory cases, oncologists order Foundation Medicine CDx to search for “off-label” therapeutic options or to identify eligibility for ongoing clinical trials. The comprehensive report generated by the test matches the patient’s specific genomic alterations with active clinical trials worldwide, providing new hope and therapeutic directions for patients who have exhausted conventional treatment pathways.

Rare or Atypical Malignancies

Rare cancers and atypical tumors often lack established, standardized treatment guidelines, making clinical management highly challenging. Performing comprehensive genomic profiling via Foundation Medicine CDx allows physicians to uncover actionable mutations that are typically associated with more common tumor types. For example, detecting an NTRK gene fusion in a rare salivary gland tumor or a sarcoma opens up the possibility of using highly effective, tumor-agnostic TRK inhibitors, transforming the therapeutic approach for rare diseases.

What Does a Foundation Medicine CDx Test Detect?

The Foundation Medicine CDx test is designed to detect a wide array of clinically actionable genomic alterations and signatures across 324 genes. Specifically, the test identifies:

• EGFR Mutations: Activating mutations (such as Exon 19 deletions and L858R point mutations) and resistance mutations (such as T790M and C797S) in non-small cell lung cancer.
• ALK Gene Rearrangements: Fusions of the ALK gene, which are highly responsive to ALK inhibitors.
• ROS1 and RET Fusions: Oncogenic fusions that serve as therapeutic targets in lung and thyroid cancers.
• BRAF Mutations: Particularly the V600E mutation, which is actionable in melanoma, colorectal cancer, and non-small cell lung cancer.
• KRAS and NRAS Mutations: Critical biomarkers in colorectal cancer that predict resistance to anti-EGFR monoclonal antibodies.
• HRAS Mutations: Alterations that can guide targeted therapies in head and neck squamous cell carcinomas.
• BRCA1 and BRCA2 Alterations: Somatic and germline-like mutations that dictate sensitivity to PARP inhibitors in breast, ovarian, prostate, and pancreatic cancers.
• PIK3CA Mutations: Activating mutations that guide the use of PI3K inhibitors in hormone receptor-positive, HER2-negative advanced breast cancer.
• ERBB2 (HER2) Amplifications and Mutations: Copy number amplifications and point mutations that guide anti-HER2 targeted therapies in breast, gastric, and lung cancers.
• MET Alterations: Including MET Exon 14 skipping mutations and high-level MET amplifications.
• NTRK1, NTRK2, and NTRK3 Fusions: Targetable genomic rearrangements that qualify patients for tumor-agnostic TRK inhibitors.
• KIT and PDGFRA Mutations: Essential for guiding tyrosine kinase inhibitor therapy in gastrointestinal stromal tumors (GIST).
• FGFR1, FGFR2, and FGFR3 Alterations: Fusions, mutations, and amplifications relevant in cholangiocarcinoma and urothelial carcinoma.
• IDH1 and IDH2 Mutations: Actionable alterations in cholangiocarcinoma and gliomas.
• Tumor Mutational Burden (TMB): A genomic signature measuring the number of somatic mutations per megabase of sequenced DNA, predicting response to immunotherapies.
• Microsatellite Instability (MSI): Evaluation of mismatch repair deficiency, identifying candidates for pembrolizumab and other checkpoint inhibitors.
• Loss of Heterozygosity (LOH): A genomic signature evaluated in ovarian cancer to assess homologous recombination deficiency (HRD).
• PTEN Loss or Mutations: Alterations in the PI3K/AKT/mTOR pathway that influence therapeutic resistance.
• AKT1, AKT2, and AKT3 Alterations: Targetable mutations in the AKT pathway.
• ATM and PALB2 Mutations: DNA damage repair gene alterations that may indicate sensitivity to DNA-damaging agents or PARP inhibitors.

Turnaround Time and Report Access at Chughtai Lab

Due to the highly complex nature of next-generation sequencing and the logistics of international shipping, the turnaround time for the Foundation Medicine CDx test is typically 14 to 21 days from the date the tissue sample is received and verified at Chughtai Lab’s central facility. Chughtai Lab employs a dedicated molecular diagnostics coordination team that handles all customs clearances, international transport protocols, and communication with the testing facility in the United States to minimize any potential delays.

Once the comprehensive genomic profiling report is finalized by Foundation Medicine’s clinical genomicists, it is delivered securely to Chughtai Lab. The report is immediately made available to the referring oncologist and the patient. Chughtai Lab provides digital access to reports through their secure online portal and mobile application, allowing patients and physicians to download and review the highly detailed, multi-page document. The report includes a clear summary of actionable genomic alterations, matched FDA-approved therapies, potential clinical trials, and a detailed scientific discussion of the findings to facilitate collaborative clinical decision-making.

Foundation Medicine CDx Findings Overview

Structure / Parameter Evaluated	Normal Findings	Possible Abnormal Findings
EGFR Gene Status	Wild-type (No pathogenic alteration detected)	Activating mutations (Exon 19 del, L858R) or resistance mutations (T790M)
ALK Gene Status	No rearrangement or fusion detected	Pathogenic ALK fusions (e.g., EML4-ALK), indicating TKI sensitivity
BRCA1 & BRCA2 Genes	No pathogenic somatic or germline-like alterations	Pathogenic frameshift, nonsense, or missense mutations indicating HRD
Tumor Mutational Burden (TMB)	Low TMB (< 10 mutations per megabase)	High TMB (≥ 10 mutations per megabase), indicating immunotherapy eligibility
Microsatellite Instability (MSI)	Microsatellite Stable (MSS)	Microsatellite Instability-High (MSI-H), indicating mismatch repair deficiency
PIK3CA Gene Status	Wild-type (No mutation detected)	Activating mutations in kinase or helical domains (e.g., H1047R, E545K)
NTRK1/2/3 Genes	No gene fusions detected	Pathogenic NTRK fusions, predicting response to larotrectinib or entrectinib
ERBB2 (HER2) Gene	Normal copy number; no pathogenic mutations	ERBB2 gene amplification or activating mutations

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 Foundation Medicine CDx?

• Experienced Healthcare Professionals: Chughtai Lab features a team of highly qualified histopathologists and molecular biologists who carefully review every tissue sample before international dispatch.
• Seamless International Logistics: The lab manages the entire secure, temperature-controlled transport process, ensuring sample integrity is maintained from Pakistan to the testing facility.
• Patient-Focused Care: Dedicated coordinators guide patients and their families through the documentation, consent, and sample collection processes, reducing administrative stress.
• Quality Diagnostic Services: Chughtai Lab is renowned for its commitment to international standards of quality control and diagnostic precision.
• Professional Reporting: Reports are delivered securely and promptly to both the patient and the referring oncologist, ensuring immediate clinical utility.
• Modern Diagnostic Approach: By facilitating advanced genomic tests like Foundation Medicine CDx, Chughtai Lab remains at the forefront of precision medicine in Pakistan.
• Convenient Location and Access: With a vast network of collection centers across Pakistan, patients can easily submit samples and coordinate testing from any major city.
• Commitment to Accurate Diagnosis: Chughtai Lab’s rigorous internal pathology review minimizes the risk of sample rejection, saving valuable time for critical cancer patients.