Foundation Medicine Heme Test in Pakistan at Chughtai Lab

Foundation Medicine Heme at Chughtai Lab

FoundationOne Heme is a comprehensive genomic profiling (CGP) service designed specifically for hematologic malignancies, including leukemia, lymphoma, and myeloma, as well as pediatric and adult sarcomas. Developed by Foundation Medicine and offered in Pakistan through Chughtai Lab, this advanced molecular diagnostic test utilizes next-generation sequencing (NGS) technology to detect all classes of genomic alterations. By analyzing the coding regions of over 400 genes via DNA sequencing and selecting RNA transcripts across more than 250 genes for rearrangements and fusions, FoundationOne Heme provides oncologists and hematologists with clinically actionable insights to guide personalized cancer treatment. This dual-method approach is particularly critical for hematologic cancers and sarcomas, which are frequently driven by complex chromosomal translocations and gene fusions that standard DNA-only sequencing assays may fail to detect.

Understanding the molecular landscape of hematologic malignancies is essential for modern precision medicine. Traditional diagnostic methods, such as morphology, flow cytometry, immunohistochemistry, and cytogenetics (including karyotyping and fluorescence in situ hybridization, or FISH), remain fundamental but often provide an incomplete picture of a tumor’s genetic profile. FoundationOne Heme complements these conventional techniques by offering a high-resolution, comprehensive view of the tumor genome in a single assay. This eliminates the need for sequential, single-gene testing, which can deplete valuable, limited clinical specimens and delay critical treatment decisions. The test identifies base substitutions, insertions and deletions (indels), copy number alterations (CNAs), and genomic rearrangements, aligning these findings with FDA-approved targeted therapies, immunotherapies, and open clinical trials globally.

The diagnostic value of FoundationOne Heme lies in its ability to refine prognostic risk stratification, confirm challenging diagnoses, and identify novel therapeutic pathways. For patients facing refractory or relapsed hematologic diseases, this genomic profile can reveal targetable mutations that would otherwise remain undetected, offering hope through off-label therapeutic options or enrollment in international clinical trials. Chughtai Lab, as a leading diagnostic network in Pakistan, facilitates this advanced testing by ensuring meticulous sample handling, cold-chain logistics, and expert clinical coordination, bringing world-class genomic medicine directly to patients and oncologists across the country.

Clinical Procedure: What to Expect

Patient Preparation

Proper patient preparation and meticulous documentation are essential to ensure the success of the FoundationOne Heme test. Because this is a highly specialized molecular assay, patients and referring physicians must adhere to the following preparation guidelines:

• Clinical Documentation: A fully completed Foundation Medicine requisition form, signed by the referring oncologist or hematologist, is mandatory. This form must include detailed clinical history, diagnosis, and specific specimen details.
• Pathology Reports: Copies of the most recent pathology reports, bone marrow aspirate reports, flow cytometry results, and relevant cytogenetic reports must be submitted alongside the sample.
• Consent Form: A signed patient consent form for genomic profiling and international sample shipment must be completed.
• No Fasting Required: If the sample is to be collected via peripheral blood, there are no dietary restrictions or fasting requirements. Patients should remain well-hydrated.
• Specimen Coordination: For bone marrow aspirates or tissue blocks, Chughtai Lab coordinators will work directly with the hospital or pathology department where the procedure was performed to retrieve the appropriate specimen.

During the Procedure

The procedure for FoundationOne Heme primarily revolves around specimen collection, quality control, and international logistics. Depending on the patient’s clinical presentation, the sample may be obtained in one of three ways:

• Peripheral Blood Collection: If the patient has a high circulating tumor burden (such as active leukemia with circulating blasts), a standard venipuncture is performed at a Chughtai Lab collection center. Approximately 2 tubes of peripheral blood (EDTA) are collected.
• Bone Marrow Aspirate: For many leukemias and myelodysplastic syndromes, a bone marrow aspirate is the preferred specimen. This procedure is performed by a qualified clinical hematologist under local anesthesia. Chughtai Lab provides specialized collection tubes containing appropriate preservatives to maintain nucleic acid stability.
• Formalin-Fixed Paraffin-Embedded (FFPE) Tissue: For lymphomas and solid tumors like sarcomas, an FFPE tissue block or unstained slides cut from the block are required. Chughtai Lab’s histopathology department reviews the block to ensure it meets the strict surface area and tumor nuclei percentage requirements (ideally greater than 20% tumor content) before shipment.
• Logistics and Shipping: Once collected, the specimen is processed under strict temperature-controlled conditions at Chughtai Lab’s central reference laboratory in Lahore. It is then packaged in specialized diagnostic shippers and sent via expedited international courier to the Foundation Medicine laboratory for sequencing.
• Safety and Comfort: Peripheral blood collection is a routine, low-risk procedure. Bone marrow aspiration may cause temporary discomfort, which is managed by the performing clinician. Chughtai Lab ensures that all steps of sample handling adhere to international biosafety and quality standards.

When is a Foundation Medicine Heme Test Performed?

Acute Myeloid Leukemia (AML) Diagnosis and Risk Stratification

In Acute Myeloid Leukemia, determining the precise molecular subtype is critical for establishing prognosis and selecting the optimal therapeutic strategy. Physicians request FoundationOne Heme at the time of initial diagnosis or relapse to identify key mutations in genes such as FLT3, NPM1, CEBPA, IDH1, IDH2, and TP53. These genetic markers dictate the European LeukemiaNet (ELN) risk classification, helping clinicians decide whether a patient requires standard chemotherapy, targeted inhibitors (such as midostaurin or gilteritinib), or an early allogeneic stem cell transplant.

Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms (MPN)

Myelodysplastic syndromes and myeloproliferative neoplasms are clonal hematopoietic disorders characterized by cytopenias or cytoses and a risk of transformation to acute leukemia. FoundationOne Heme is performed to detect somatic mutations in genes like JAK2, CALR, MPL, SF3B1, ASXL1, and RUNX1. Identifying these mutations assists in confirming a clonal disorder, distinguishing it from reactive causes, assessing the risk of leukemic transformation, and guiding the use of targeted therapies such as JAK inhibitors.

Refractory or Relapsed Lymphomas

Patients with aggressive lymphomas, such as Diffuse Large B-Cell Lymphoma (DLBCL), Follicular Lymphoma, or Mantle Cell Lymphoma, who have failed first-line immunochemotherapy require comprehensive genomic profiling. FoundationOne Heme is utilized to identify underlying oncogenic drivers, gene fusions (such as MYC, BCL2, or BCL6 rearrangements), and mutations in pathways like NF-kB or JAK/STAT. This information helps oncologists identify eligibility for novel targeted agents, clinical trials, or cellular therapies like CAR-T.

Multiple Myeloma Targeted Therapy Selection

In Multiple Myeloma, genomic instability is a hallmark of disease progression. While standard cytogenetics and FISH detect common translocations, FoundationOne Heme provides a deeper analysis of somatic mutations (e.g., KRAS, NRAS, BRAF, TP53) and copy number alterations. This test is performed in relapsed or refractory settings to identify targetable mutations, such as BRAF V600E, or to evaluate eligibility for clinical trials evaluating novel small-molecule inhibitors and immunotherapies.

Sarcomas and Rare Mesenchymal Tumors

Sarcomas are highly complex tumors that often present diagnostic challenges due to overlapping histological features. Because many sarcomas are characterized by pathognomonic gene fusions, the RNA-sequencing component of FoundationOne Heme is uniquely suited for these cases. The test is performed to detect diagnostic fusions (such as EWSR1-FLI1 in Ewing sarcoma or SS18-SSX in synovial sarcoma) and to identify potential therapeutic targets, such as NTRK fusions, which can be treated with highly effective TRK inhibitors.

What Does a Foundation Medicine Heme Test Detect?

FoundationOne Heme is designed to detect a wide spectrum of genomic alterations across clinically relevant genes. The comprehensive assay detects:

• FLT3 Mutations: Internal tandem duplications (ITD) and tyrosine kinase domain (TKD) mutations, which are critical prognostic and therapeutic markers in AML.
• NPM1 Mutations: Frameshift mutations that generally confer a favorable prognosis in AML in the absence of FLT3-ITD.
• IDH1 and IDH2 Mutations: Recurrent mutations that create an oncometabolite, targetable by specific IDH inhibitors like ivosidenib and enasidenib.
• TP53 Alterations: Mutations and deletions associated with therapeutic resistance and poor prognosis across multiple hematologic malignancies.
• JAK2 V617F and Exon 12 Mutations: Diagnostic markers for polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
• CALR and MPL Mutations: Key driver mutations in JAK2-negative myeloproliferative neoplasms.
• SF3B1, SRSF2, and U2AF1 Mutations: Splicing factor mutations common in myelodysplastic syndromes, associated with specific clinical phenotypes like ring sideroblasts.
• ASXL1, TET2, and DNMT3A Mutations: Epigenetic regulators frequently mutated in clonal hematopoiesis and myeloid malignancies.
• RUNX1 Alterations: Transcription factor mutations associated with familial platelet disorders and high-risk myeloid neoplasms.
• BCR-ABL1 Gene Fusion: The diagnostic hallmark of Chronic Myeloid Leukemia (CML) and a critical prognostic marker in Acute Lymphoblastic Leukemia (ALL).
• PML-RARA Gene Fusion: The diagnostic translocation of Acute Promyelocytic Leukemia (APL), guiding emergency therapy with ATRA and arsenic trioxide.
• MYC, BCL2, and BCL6 Rearrangements: Essential for identifying “double-hit” or “triple-hit” high-grade B-cell lymphomas.
• KMT2A (MLL) Rearrangements: High-risk translocations found in infant and therapy-related leukemias.
• EZH2 Mutations: Targetable epigenetic alterations in follicular lymphoma and diffuse large B-cell lymphoma.
• BRAF V600E Mutations: Therapeutic targets in hairy cell leukemia, Langerhans cell histiocytosis, and multiple myeloma.
• KIT Mutations: Critical for prognosis in core-binding factor AML and diagnostic/therapeutic targeting in systemic mastocytosis.
• NTRK1, NTRK2, and NTRK3 Fusions: Highly targetable fusions across various solid tumors and sarcomas.
• FGFR1, PDGFRA, and PDGFRB Fusions: Associated with myeloid and lymphoid neoplasms with eosinophilia, targetable with tyrosine kinase inhibitors.
• Tumor Mutational Burden (TMB): An FDA-approved biomarker that measures the number of somatic mutations per megabase, predicting response to immune checkpoint inhibitors.
• Microsatellite Instability (MSI): Evaluates mismatch repair deficiency, which serves as a predictor for immunotherapy efficacy.

Turnaround Time and Report Access at Chughtai Lab

The turnaround time for FoundationOne Heme at Chughtai Lab is typically 14 to 21 days from the date of sample collection. This timeline is required due to the complex nature of international shipping, strict quality control checks, high-throughput next-generation sequencing, and comprehensive bioinformatic analysis performed at Foundation Medicine’s state-of-the-art facilities. Chughtai Lab ensures that the cold chain is meticulously maintained throughout transit to preserve the integrity of the DNA and RNA molecules.

Once the genomic analysis is complete, a highly detailed, clinically annotated report is generated. This report lists all detected genomic alterations, classifies them by clinical significance, and aligns them with potential FDA-approved therapies, clinical trials, and prognostic implications. The report is delivered directly to the referring oncologist. Patients and physicians can also access the report securely online through the Chughtai Lab web portal or the Chughtai Lab mobile application, ensuring rapid access to critical diagnostic data to expedite treatment planning.

Foundation Medicine Heme Findings Overview

Structure / Parameter Evaluated	Normal Findings	Possible Abnormal Findings
DNA Substitutions and Indels	No pathogenic mutations detected	Detection of targetable mutations (e.g., FLT3-ITD, IDH1/2, BRAF V600E) guiding specific therapy.
Gene Fusions / Rearrangements (RNA)	No oncogenic fusions or translocations detected	Identification of diagnostic fusions (e.g., BCR-ABL1, PML-RARA, EWSR1-FLI1) confirming disease subtype.
Copy Number Alterations (CNAs)	Normal diploid gene copy number	Gene amplifications or homozygous deletions (e.g., CDKN2A/B deletion, MYC amplification).
Tumor Mutational Burden (TMB)	Low TMB (fewer mutations per megabase)	High TMB, indicating a high neoantigen load and potential benefit from immunotherapy.
Microsatellite Instability (MSI)	Microsatellite Stable (MSS)	Microsatellite Instability-High (MSI-H), suggesting mismatch repair deficiency.
Splicing Factor Genes	Wild-type sequence (no mutations)	Mutations in SF3B1, SRSF2, or U2AF1, confirming myelodysplastic syndrome or clonal hematopoiesis.
Epigenetic Regulators	Wild-type sequence (no mutations)	Mutations in DNMT3A, TET2, or ASXL1, indicating clonal evolution or adverse prognostic risk.
Tumor Suppressor Genes	Intact tumor suppressor pathways	Inactivating mutations or deletions in TP53, RB1, or PTEN, associated with chemotherapy resistance.

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 Heme?

• Experienced Healthcare Professionals: Chughtai Lab employs a team of highly trained molecular pathologists, technologists, and clinical coordinators dedicated to advanced genomic diagnostics.
• Patient-Focused Care: The lab provides comprehensive support throughout the testing process, assisting patients with documentation, consent, and sample collection.
• Quality Diagnostic Services: Adherence to international standards ensures that every sample is handled with the highest level of precision and quality control.
• Seamless International Logistics: Chughtai Lab manages the entire shipping and customs clearance process, ensuring samples reach Foundation Medicine safely and within temperature specifications.
• Comprehensive Reporting: Patients receive a detailed, easy-to-understand genomic profile that directly aids oncologists in clinical decision-making.
• Modern Diagnostic Approach: By partnering with global leaders like Foundation Medicine, Chughtai Lab brings cutting-edge precision oncology to Pakistan.
• Convenient Location and Access: With a vast network of collection centers across Pakistan, patients can easily submit samples or coordinate retrieval from local hospitals.
• Commitment to Accurate Diagnosis: Chughtai Lab’s dedication to diagnostic excellence ensures reliable, reproducible, and clinically actionable results for complex cancer cases.