Somatic Solid Tumor Expanded Panel at Chughtai Lab

Somatic Solid Tumor Expanded Panel at Chughtai Lab

The Somatic Solid Tumor Expanded Panel at Chughtai Lab represents a paradigm shift in modern oncology, transitioning cancer care from a generalized treatment model to highly personalized precision medicine. This advanced molecular diagnostic test utilizes state-of-the-art Next-Generation Sequencing (NGS) technology to analyze the genomic profile of a patient’s tumor. By examining a comprehensive panel of genes, this test identifies somatic mutations—genetic alterations that occur specifically within the tumor cells during a person’s lifetime and are not inherited. Understanding these specific genetic drivers allows oncologists to pinpoint the exact molecular mechanisms fueling the malignancy, enabling the selection of highly targeted therapies, predicting response to immunotherapy, and identifying potential clinical trials.

Somatic solid tumor testing is performed on biopsy or surgical resection tissue, specifically Formalin-Fixed Paraffin-Embedded (FFPE) tissue blocks. The genomic analysis evaluates key alterations, including Single Nucleotide Variants (SNVs), small insertions and deletions (indels), Copy Number Variants (CNVs), and gene fusions or rearrangements. The clinical utility of this expanded panel is profound. It provides critical diagnostic, prognostic, and therapeutic insights across a wide range of solid tumors, including lung, breast, colorectal, ovarian, prostate, and brain cancers. By partnering with GeneTech, a pioneer in molecular diagnostics, Chughtai Lab ensures that patients across Pakistan have access to world-class genomic profiling, helping to optimize treatment outcomes and avoid the physical and financial toll of ineffective standard chemotherapies.

Clinical Procedure: What to Expect

Patient Preparation

Because the Somatic Solid Tumor Expanded Panel is performed on tumor tissue previously obtained during a biopsy or surgical procedure, there is typically no direct physical preparation required from the patient. However, ensuring the success of this highly complex molecular test requires careful coordination and preparation of clinical materials:

• Tissue Sample Retrieval: Patients or their healthcare providers must arrange for the retrieval of the Formalin-Fixed Paraffin-Embedded (FFPE) tissue block and the corresponding histopathology slides from the laboratory where the initial biopsy or surgery was processed.
• Histopathology Report: A copy of the original histopathology report must accompany the tissue sample. This report provides essential context, including the tumor site, histological diagnosis, and tumor cell cellularity.
• Sample Adequacy: The tissue block must contain a sufficient percentage of tumor cells (typically a minimum of 20% to 30% tumor content) to ensure accurate DNA and RNA extraction. If the tumor content is low, a pathologist may perform macrodissection to enrich the sample.
• Clinical History: Providing a detailed clinical history, including previous cancer treatments (such as chemotherapy, radiation, or targeted therapies), is crucial, as prior therapies can influence the tumor’s genomic profile and the interpretation of the results.
• No Fasting Required: If a concurrent blood sample is requested for germline comparison or liquid biopsy, no fasting or special dietary restrictions are necessary prior to the blood draw.

During the Procedure

The analytical process for the Somatic Solid Tumor Expanded Panel is highly sophisticated and takes place within specialized molecular genetics laboratories. Once the FFPE tissue block is received at Chughtai Lab, the procedure follows a rigorous, multi-step scientific workflow:

• Pathology Review: A consultant pathologist reviews the hematoxylin and eosin (H&E) stained slides to confirm the diagnosis, assess the quality of the tissue, and demarcate areas with high tumor cellularity for nucleic acid extraction.
• DNA and RNA Extraction: The marked areas of the tumor tissue are carefully microdissected from the slide or block. Specialized chemical processes are used to deparaffinize the tissue, lyse the cells, and extract high-quality DNA and RNA.
• Library Preparation and Target Enrichment: The extracted nucleic acids undergo library preparation, where they are fragmented, and specific adapters are attached. Target enrichment is performed to capture and amplify the specific regions of interest (the exons of the genes included in the expanded panel).
• Next-Generation Sequencing (NGS): The prepared libraries are loaded onto high-throughput NGS sequencers. The instrument sequences millions of DNA and RNA fragments simultaneously, generating massive amounts of raw genomic data.
• Bioinformatics Analysis: Advanced computational algorithms and bioinformatics pipelines align the sequenced reads to the human reference genome. Specialized software identifies genetic variants, filters out benign polymorphisms, and highlights clinically significant somatic mutations.
• Clinical Interpretation and Reporting: A team of molecular pathologists and geneticists evaluates the identified variants against global oncology databases to determine their clinical relevance, matching mutations with FDA-approved targeted therapies, resistance profiles, and active clinical trials.

When is a Somatic Solid Tumor Expanded Panel Performed?

Advanced or Metastatic Malignancies

Oncologists frequently request the Somatic Solid Tumor Expanded Panel for patients diagnosed with advanced, recurrent, or metastatic (Stage III or IV) solid tumors. In these late-stage cancers, standard treatment protocols may have been exhausted, or the cancer may have progressed despite first-line chemotherapy. The expanded panel helps identify “actionable” mutations that can be targeted with specific, highly effective novel drugs, offering new therapeutic avenues and extending survival for patients who otherwise have limited options.

First-Line Therapy Selection in Specific Cancers

For certain cancer types, such as non-small cell lung cancer (NSCLC), metastatic colorectal cancer, and advanced breast cancer, genomic profiling is now recommended as part of the initial diagnostic workup. Identifying specific mutations (such as EGFR mutations or ALK fusions in lung cancer) before initiating treatment is critical, as targeted therapies are significantly more effective and less toxic than traditional chemotherapy as first-line options.

Evaluation for Immunotherapy Eligibility

Immunotherapy has revolutionized cancer treatment, but it is highly effective only in a subset of patients. The Somatic Solid Tumor Expanded Panel evaluates critical genomic biomarkers, such as Microsatellite Instability (MSI) status and Tumor Mutational Burden (TMB). Patients whose tumors exhibit High Microsatellite Instability (MSI-H) or a High Tumor Mutational Burden (TMB-H) are excellent candidates for immune checkpoint inhibitors, such as pembrolizumab, which help the body’s immune system recognize and destroy cancer cells.

Detecting Mechanisms of Treatment Resistance

Cancers are highly dynamic and can evolve over time, developing resistance to targeted therapies that were previously effective. When a patient’s tumor begins to progress while on a targeted drug, a repeat biopsy and expanded genomic profiling can identify secondary resistance mutations (such as the EGFR T790M or C797S mutations in lung cancer). Identifying these resistance mechanisms allows oncologists to switch patients to next-generation targeted drugs designed to bypass these specific mutations.

Unusual, Rare, or Histologically Ambiguous Tumors

When a patient is diagnosed with a rare cancer or a tumor that does not fit standard histological classifications, determining the optimal treatment pathway can be exceptionally challenging. The Somatic Solid Tumor Expanded Panel can reveal the underlying molecular signature of the tumor, helping to classify the malignancy more accurately and identifying therapeutic targets that may have been successful in other tumor types sharing the same genetic alteration.

What Does a Somatic Solid Tumor Expanded Panel Detect?

The Somatic Solid Tumor Expanded Panel is designed to detect a comprehensive array of genetic alterations across hundreds of cancer-related genes. Key findings and molecular markers identified by this panel include:

• EGFR Mutations: Activating mutations in exons 19 and 21 (e.g., L858R) and resistance mutations (e.g., T790M, C797S) in non-small cell lung cancer, guiding EGFR tyrosine kinase inhibitor (TKI) therapy.
• ALK Gene Rearrangements: Fusions of the ALK gene (most commonly EML4-ALK) in lung adenocarcinoma, indicating high sensitivity to ALK inhibitors like crizotinib and alectinib.
• ROS1 and RET Fusions: Oncogenic fusions that serve as therapeutic targets for specific tyrosine kinase inhibitors in lung and thyroid cancers.
• NTRK1, NTRK2, and NTRK3 Fusions: Rare but highly actionable fusions across various solid tumors, qualifying patients for tumor-agnostic TRK inhibitors.
• KRAS Mutations: Mutations in codons 12, 13, and 61 (including KRAS G12C) that predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer and guide targeted therapy in lung cancer.
• NRAS and HRAS Mutations: Alterations in the RAS pathway that influence treatment decisions in colorectal cancer and melanoma.
• BRAF V600E Mutations: Common in melanoma, colorectal cancer, and thyroid cancer, indicating eligibility for combined BRAF and MEK inhibitor therapy.
• PIK3CA Mutations: Alterations in the PI3K/AKT/mTOR pathway, particularly relevant in hormone receptor-positive, HER2-negative breast cancers.
• BRCA1 and BRCA2 Somatic Mutations: Pathogenic variants in homologous recombination repair genes, indicating eligibility for PARP inhibitors in ovarian, breast, prostate, and pancreatic cancers.
• ERBB2 (HER2) Amplifications and Mutations: Copy number gains or sequence variants in breast, gastric, and lung cancers, guiding anti-HER2 targeted therapies.
• MET Alterations: MET exon 14 skipping mutations and high-level MET gene amplifications, which are targetable in non-small cell lung cancer.
• FGFR1, FGFR2, and FGFR3 Alterations: Fusions, mutations, or amplifications in cholangiocarcinoma, urothelial carcinoma, and other solid tumors.
• KIT and PDGFRA Mutations: Primary diagnostic and therapeutic markers for gastrointestinal stromal tumors (GIST).
• IDH1 and IDH2 Mutations: Critical diagnostic and prognostic markers in gliomas and cholangiocarcinomas.
• TP53 Mutations: The most common tumor suppressor gene alteration, providing prognostic context and indicating genomic instability.
• PTEN Loss or Mutations: Alterations leading to hyperactivation of the PI3K pathway and potential resistance to certain therapies.
• Tumor Mutational Burden (TMB): A quantitative measure of the number of somatic mutations per megabase of sequenced DNA, predicting response to immunotherapy.
• Microsatellite Instability (MSI) Status: Evaluation of mismatch repair deficiency, identifying MSI-High tumors eligible for pembrolizumab.
• Homologous Recombination Deficiency (HRD) Status: A marker of genomic instability that predicts response to platinum-based chemotherapy and PARP inhibitors.
• CDK4 and CDK6 Amplifications: Alterations that suggest potential benefit from CDK4/6 inhibitors in various malignancies.
• MDM2 Amplifications: Often observed in liposarcomas and other solid tumors, indicating p53 pathway inhibition.
• AR (Androgen Receptor) Amplifications and Mutations: Relevant in advanced prostate cancer, guiding anti-androgen therapy decisions.
• ESR1 Mutations: Acquired mutations in breast cancer that confer resistance to aromatase inhibitors, guiding subsequent endocrine therapy.
• APC Mutations: Key driver mutations in colorectal cancers, helping to confirm tumor origin and pathway involvement.
• ATM and CHEK2 Mutations: DNA damage response gene alterations that may suggest sensitivity to PARP inhibitors or platinum agents.

Turnaround Time and Report Access at Chughtai Lab

Due to the highly complex nature of Next-Generation Sequencing (NGS), target enrichment, bioinformatics processing, and clinical interpretation, the turnaround time for the Somatic Solid Tumor Expanded Panel is typically 3 to 4 weeks. This timeline ensures that every sample undergoes rigorous quality control, pathology review, and comprehensive genomic analysis to deliver a highly accurate and clinically actionable report.

Chughtai Lab provides seamless and convenient access to diagnostic reports. Once the molecular pathology report is finalized, patients and their referring oncologists are notified via SMS. Reports can be accessed and downloaded digitally through the official Chughtai Lab website portal or the user-friendly Chughtai Lab Mobile App. Hard copies of the comprehensive report, which includes detailed therapeutic recommendations and clinical trial matches, can also be collected from any Chughtai Lab diagnostic center across Pakistan or delivered directly to the patient’s home.

Somatic Solid Tumor Expanded Panel Findings Overview

Structure / Parameter Evaluated	Normal Findings	Possible Abnormal Findings
EGFR Gene Status	Wild-type (No mutation detected)	Activating mutations (Exon 19 del, L858R) or resistance mutations (T790M, C797S)
ALK Gene Status	No rearrangement or fusion detected	ALK gene fusion (e.g., EML4-ALK positive), indicating sensitivity to ALK inhibitors
KRAS Gene Status	Wild-type (No mutation detected)	Pathogenic mutations (e.g., G12C, G12D, G12V), predicting resistance to anti-EGFR therapies
BRAF Gene Status	Wild-type (No mutation detected)	BRAF V600E or other pathogenic mutations, indicating eligibility for BRAF/MEK inhibitors
BRCA1 & BRCA2 Genes	No somatic mutations detected	Somatic pathogenic mutations, indicating potential benefit from PARP inhibitor therapy
Microsatellite Instability (MSI)	Microsatellite Stable (MSS)	Microsatellite Instability-High (MSI-H), indicating high likelihood of response to immunotherapy
Tumor Mutational Burden (TMB)	Low TMB (<10 mutations/megabase)	High TMB (≥10 mutations/megabase), associated with favorable response to immune checkpoint inhibitors
NTRK1/2/3 Gene Status	No fusions detected	NTRK gene fusions, indicating eligibility for tumor-agnostic TRK inhibitors

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 Somatic Solid Tumor Expanded Panel?

• Experienced Healthcare Professionals: Our team consists of highly qualified pathologists, molecular biologists, and geneticists specializing in oncology diagnostics.
• Strategic Collaboration: Partnering with GeneTech, a pioneer in molecular diagnostics, to bring cutting-edge genomic profiling to patients in Pakistan.
• State-of-the-Art Technology: Utilizing advanced Next-Generation Sequencing (NGS) platforms to ensure high sensitivity and specificity in mutation detection.
• Comprehensive Gene Coverage: The expanded panel analyzes a vast array of clinically actionable genes, maximizing the potential to find targeted treatment options.
• Rigorous Quality Control: Adhering to strict international laboratory standards and quality assurance protocols for molecular testing.
• Seamless Report Access: Convenient digital reporting through the Chughtai Lab website, mobile application, and dedicated WhatsApp services.
• Nationwide Collection Network: Patients can submit tissue samples and clinical documents at any of our numerous collection centers across Pakistan.
• Patient-Focused Care: Providing dedicated support, clear guidance on sample requirements, and compassionate service throughout the diagnostic journey.