Molecular Oncology

Molecular Oncology

MPLN’s molecular oncology diagnostics (MDX) laboratory performs quantitative polymerase chain reaction (qPCR) and Next Generation Sequencing (NGS) analyses to support therapy selection, treatment, monitoring, and minimal residual disease detection. 

Next-Generation Sequencing

Next Generation Sequencing (NGS)

NGS enables the identification of genetic sequences within an individual’s whole genome. This powerful technique is widely used in molecular oncology for classifying key gene sequences and hotspot mutations, providing context for:

IDENTIFYING:

    • Genetic alterations driving tumor biology
    • Behavior drug sensitivity or resistance
    • Disease prognosis

ENABLING:

    • Selection of the most appropriate treatment regimen
    • Timely administration of drugs
    • Safe use of therapeutics

NGS can greatly benefit patients with new diagnoses or resistance to conventional therapy and those facing complex diagnostic challenges. Furthermore, as the range of genetic mutations associated with cancer that can be targeted with treatments continues to expand, MPLN is committed to offering patients and clients the latest laboratory-developed tests (LDTs) and FDA-approved in vitro diagnostic (IVD) assays.

Targeted NGS Panels

MPLN NGS panel content is based on NCCN and updated WHO practice guidelines as clinical data and practice guidelines are evolving at a rapid pace for both solid and heme oncology disorders. Next generation sequencing (NGS) using multiplex targeted gene panels provides a practical solution for comprehensive mutation analysis in routine clinical practice. Targeted panels offered at MPLN contain relevant oncogenic driver mutations which may have therapeutic, diagnostic, or prognostic relevance to clinical patients and for clinical trial studies.

Clonality and Gene Rearrangements

NGS offers significant advantages over PCR based approaches for the detection and monitoring of lymphoproliferative T-cell and B-cell disorders. Offerings include:

  • T-cell receptor and B-cell immunoglobulin heavy chain (IgH) clonal sequencing to assist in the diagnosis of lymphomas
  • IgVH somatic hypermutation (SHM) status determination in CLL as a primary prognostic indicator for disease risk stratification

Quantitative Polymerase Chain Reaction (qPCR)

Although quantitative PCR (qPCR) based methodology is more than 20 years old, it remains a widely used and inexpensive methodology for detecting individual genetic mutations with sensitivity as low as 0.001%. At MPLN, both laboratory-developed tests (LDTs) and FDA-approved (IVD) assays are used for a wide variety of applications, including:

  • Companion diagnostics
  • Minimal residual disease testing
  • Gene-therapy monitoring

Next Generation Sequencing (NGS)

Advances in pharmacogenetics, along with the design and
development of targeted cancer therapies, have led to an
increasing number of companion diagnostic assays.

Whereas pharmacogenetics explores a patient’s specific
genotype and response to a drug, companion diagnostics is a
broader application that includes the association of biomarkers
and genetic mutations that predict treatment outcomes.

Using molecular technology, we can identify patients who may
experience adverse drug interactions or those who may be
unresponsive to certain medications due to genetic variations or
expression of specific hormones, proteins and/or enzymes.

Mutation Analysis

Identifying gene mutations and specific markers prior to
initiating therapy can result in better patient outcomes as well
as substantial cost savings by avoiding poor drug choices and
needless over prescribing.

For example, colorectal cancer (CRC) patients with KRAS or
BRAF mutations are less likely to respond to anti-EGFR therapy.
Therefore, ASCO recommends patients with metastatic CRC who
are candidates for anti-EFGR therapy be tested for KRAS gene
mutations prior to initiating treatment. Also, when the KRAS
gene is not mutated, NCCN guidelines recommend determination
of BRAF gene status as part of their workup, although this
recommendation is currently based on inconsistent field data.

Clonality and Gene Rearrangements

T-cell receptor and B-cell immunoglobulin heavy chain (IgH) or
light chain (Igk) gene rearrangement studies can be supportive
of a lymphoma diagnosis with identification of monoclonality in a
morphologically suspicious lymphoid infiltrate.

Molecular immunoglobulin kappa (Igk) light chain testing is
also a useful complement to B-cell heavy chain (IgH) gene
rearrangement analysis. Igk gene rearrangement can provide confirmation of clonality in post-germinal center (mature)
neoplasms where clonotypic IgH signatures may not be detected
due to somatic hypermutation of VH genes.

The Igk assay, in addition to identifying clonality in atypical
lymphoproliferative disorders, can also support a differential
diagnosis between reactive lesions and hematologic
malignancies, and assign presumptive lineage in mature
monoclonal lymphoproliferative disorders.

Minimal Residual Disease Detection

Detection and monitoring of minimal residual disease can
be accomplished by quantitative PCR, specifically in chronic
myelogenous leukemia and acute prolymphocytic leukemia.
Quantitative PCR provides at least 100 to 1000 times greater
sensitivity than fluorescent in situ hybridization (FISH).
Measurements are taken at baseline in newly diagnosed cases and
at regular intervals to monitor for evidence of molecular remission in
response to chemotherapy or allogeneic stem cell transplantation.

Studies using gene sequencing can also assist in identifying patients
with an acquired drug resistance to tyrosine kinase inhibitor (TKI)
therapy, and NCCN guidelines recommend consideration of ABL
Kinase domain sequencing for these patients.

Serial evaluation for quantitative BCR/ABL in a case of chronic myelogenous leukemia on Gleevec® treatment
Molecular Oncology

Molecular Diagnostic Oncology Testing

Molecular Oncology Test Diagnostic Condition & Companion Therapy
ABL kinase mutation analysis Philadelphia positive leukemia (CML, ALL, AML) and tyrosine kinase inhibitor resistance
AML mutation profile: FLT3 and NPM1 mutations with reflex to CEBPA mutation AML
BCR/ABL quantitative PCR major and minor Philadelphia positive leukemia (CML, ALL, AML), baseline, and monitoring minimal residual disease
B-cell heavy chain gene rearrangement
B-cell kappa light chain gene rearrangement
B-cell clonality
BRAF V600E mutation EGFR inhibitor response in metastatic Colorectal Cancer (CRC): Erbitux® (cetuximab), and Vectibix™ (panitumumab)
c-kit mutation AML
JAK2 V617F mutation PV
KRAS mutation EGFR inhibitor response in metastatic CRC: Erbitux, and Vectibix
MPL W515/S505N mutation EV, PMF
PML/RARA t(15;17) quantitative PCR short and long form APL, baseline and monitoring minimal residual disease
T-cell gamma receptor gene rearrangement T-cell clonality
UGT1A1 genotype Camptosar® (Irinotecan) toxicity and drug dosage in metastatic or recurrent CRC
*Fluorescence in situ hybridization (FISH) assays *Complement molecular PCR assays for diagnosis, prognosis and minimal residual disease detection
NCCN Guideline

*Fluorescence in situ hybridization (FISH) assays performed in our
Cytogenetics Laboratory complement molecular PCR assays for
diagnosis, prognosis and minimal residual disease detection of
hematological malignancies and solid tumors. Clinical indications
and/or results from previous testing are utilized to select specific
gene locations for investigation. FISH uses fluorescent probes that
bind to only those parts of the chromosome with which they show a
high degree of sequence similarity.

For a complete list of FISH probes available to detect and localize the
presence or absence of specific DNA sequences on
chromosomes in metaphase, interphase cells or in tissue, visit us
online at www.MPLNET.com.

References
1. Ross J S et al. (2004). Targeted Therapies for Cancer 2004. Am J Clin Pathol.122(4):598-609.

Trademarks
Gleevec is a registered trademark of Novartis Pharmaceuticals Corporatiwon.
Erbitux is a registered trademark of Imclone systems, Inc.
Vectibix is a trademark of Amgen, Inc.
Camptosar is a registered trademark of Pfizer, Inc

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    Project Management

    Our project managers have strong scientific backgrounds and extensive experience in complex research-based clinical trials. They collaborate with our scientific operations, client services, and commercial operations teams to deliver high-quality, regulatory-compliant testing results on time at every project step.

    Key Features

    • Each study is assigned a dedicated and experienced project manager
    • Studies are typically set up within 6 to 8 weeks of contract signature
    • Project management software tools ensure timely deliveries
    • Onsite customer service teams efficiently resolve queries and deliver reports

    Benefits

    • Accelerated study setup time
    • Responsive communication with the scientific and operational team
    • Testing completed on time and within budget
    • Prompt reporting of critical study data

    Data Management

    The key to a successful clinical trial is accurate, clean, quality data. Our team of data managers provides you with data in customized formats exported to your data management teams from our in-house laboratory information system (LIS).

    Key Features

    • Access to dedicated and experienced data specialists upon contract award
    • Customized reports are agreed upon in study-specific data transfer agreement
    • In-house software development team for custom data solutions
    • Flexible data exports and data transfers

    Benefits

    • Real-time reports for your data and project teams to aid in patient management
    • Guaranteed data integrity and quality
    • Improved decision-making and enhanced patient safety
    • Timely access to accurate, clean data for intermediate or final database lock
    Genomic Solutions

    Genomic Solutions

    Genomic medicine, a vital tool in oncology and drug development by providing deeper, more personalized insights into each patient.

    Beyond informing drug target discovery, validation, and clinical development, it uncovers critical genetic markers that drive disease progression and influence individual treatment responses. This empowers healthcare professionals to create more precise, tailored treatment plans, optimizing medical management based on each patient’s genetic profile.

    DNA Solutions – WGS*, WGMS*, WES*, TSO-500 Comp, Pillar OncoReveal
    RNA Solutions – Total RNA-Seq*, RNA exome*, mRNA*
    Liquid Biopsy Solutions – TSO-500 ctDNA, PGDx elio™ plasma complete*

    Key Features

    • Targeted NGS panels, including FDA-approved assays with companion diagnostic designations
    • Customized bioinformatics and reporting solutions 
    • Robust assay designs to accommodate low-yielding biopsy material
    • Streamlined wet lab processes to meet screening window timelines

    Benefits

    • Identify variants along with key biomarker signatures
    • Save time and money by assessing multiple biomarkers in a single test
    • Enable targeted therapies with actionable, easy-to-interpret results
    • Assists in targeted patient stratification and recruitment
    • Accelerates the development of personalized medicine

    *Offered through fully accredited partner laboratories.

    Digital Pathology

    Digital Pathology

    Digital pathology revolutionizes clinical trials by enhancing accessibility, cost-efficiency, compliance, and data management. MPLN’s comprehensive digital pathology services streamline clinical research, allowing for improved patient outcomes and operational efficiency.

    Key Features

    • Seamless access to digital slides and slide retrieval enables instant access to digital slides.
    • Cost-effective digital slide management streamlines logistics by reducing the need for physical slide storage and transportation.
    • Digital storage ensures slides remain in perfect condition over time.

    Benefits

    • Allows key opinion leaders (KOL) and remote client pathologists to be utilized
    • Digital slides can be easily shared, allowing for faster, more collaborative decisions, including obtaining second opinions.
    • Reduces the costs associated with physical storage and transport of slides, improving trial efficiency.
    • Simplifies regulatory processes, ensuring quicker and more accurate FDA submissions and audit readiness.
    • Prevents slide degradation or breakage, maintaining the quality of research data for the long term.
    • Enables broader patient recruitment by facilitating decentralized clinical trials for wider geographic participation, increasing patient recruitment and diversity.
    Global Logistics

    Global Logistics

    Effective global logistics are the cornerstone of effective specialty laboratory testing supporting global clinical trials. With precious patient samples such as biopsy and bone marrow aspirates, ensuring samples reach the lab on time and within stability is paramount.

    Key Features

    • Partnerships with global specialist couriers and large integrators to support global studies and specialty shipping requirements
    • Ambient, refrigerated, frozen, and liquid nitrogen storage and shipment services available
    • Real-time or batched shipments based on your clinical trial’s individual needs
    • Secure, high-volume, redundant data storage solutions for digital pathology images
    • Expert advice for effective sample collection, handling, and transport
    • Accurate tracking and inventory for all clinical trial specimens

    Benefits

    • Safe and effective transport of specimens worldwide
    • Standardized procedures to reduce pre-analytical variability and ensure valid results
    • Centralized and harmonized specialty pathology testing supported
    • Reduced costs and maximized budgets with fully managed logistics from one trusted source
    • Readily available inventories, manifests, and shipments for timely study closeouts
    Multiplex IHC clinical trial services

    IHC & Multiplex IHC

    Our advanced technology enables simultaneous visualization of single or multiple biomarkers within the same tissue section, delivering comprehensive insights and precise diagnostics. With unmatched expertise and cutting-edge technology, our team supports you in understanding complex tissue microenvironments, aiding patient stratification and treatment response prediction.

    Key Features

    • Simultaneously visualize multiple biomarkers within the same tissue section for deeper insights.
    • Advanced analysis of tissue microenvironments to assist in patient stratification and treatment response prediction.
    • Custom assay design and flexible testing to meet your unique research or clinical trial needs.
    • Our expert team provides detailed data analysis and interpretation to ensure accurate results.

    Benefits

    • Allows enhanced information from small biopsy samples. (I.e. NSCLC)
    • Gain comprehensive insights that lead to more precise diagnostics and better patient outcomes.
    • Enhanced ability to identify patient subgroups and better predict treatment responses more accurately.
    • Whether in biomarker discovery or clinical trials, our advanced technology supports a range of applications, helping you unlock the full potential of your tissue samples.
    Cytogenetics FISH - clinical trial services

    Cytogenetics & FISH

    We offer a comprehensive range of chromosome analysis and fluorescent in situ hybridization (FISH) testing with industry-leading turnaround times and global coverage. Our board-certified lab directors and experienced cytogenetic technologists ensure accurate, efficient, and competitively priced testing with the highest quality of service.

    Key Features

    • Extensive FISH menu of over 40 loci and disease-specific panels detecting gene amplifications, deletions, translocations, and inversions.
    • Testing is available on bone marrow, blood, and FFPE tissue samples.
    • Specialized Offerings:
      • Plasma cell enrichment for plasma disorders
      • Stat turnaround for PML::RARA and acute myeloid leukemia
      • Bladder cancer urine analysis
      • Custom FISH assay development
    • Comprehensive chromosome analysis testing for oncology, infertility, recurrent pregnancy loss, and congenital disorders.
    • Global coverage of equivocal CAP/CLIA services supporting clinical trials

    Benefits

    • Rapid, precise results critical for diagnosis and treatment.
    • Expert-driven testing with Board-certified experts ensures the highest accuracy.
    • Tailored assays and solutions to meet unique clinical needs.
    • Faster diagnostics support timely treatment decisions.