Pdgfr Blood Test

[Beatrix Gerke]

ThePDGFRA gene provides instructions for making a protein called platelet-derived growth factor receptor alpha (PDGFRA), which is part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The PDGFRA protein is found in the cell membrane of certain cell types where a specific protein, called platelet-derived growth factor, attaches (binds) to it. This binding turns on (activates) the PDGFRA protein, which then activates other proteins inside the cell by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions (a process called phosphorylation). This process leads to the activation of a series of proteins in multiple signaling pathways.

The signaling pathways stimulated by the PDGFRA protein control many important cellular processes such as cell growth and division (proliferation) and cell survival. PDGFRA protein signaling is important for the development of many types of cells throughout the body.

Genetic abnormalities that involve the PDGFRA gene cause a type of blood cell cancer called PDGFRA-associated chronic eosinophilic leukemia. This condition is characterized by an increased number of eosinophils, a type of white blood cell involved in allergic reactions. These genetic abnormalities are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells. The most common of these genetic abnormalities is a deletion of genetic material from chromosome 4 that brings together parts of two genes, FIP1L1 and PDGFRA, creating the FIP1L1-PDGFRA fusion gene. Occasionally, genes other than FIP1L1 are fused with the PDGFRA gene. Mutations that change single DNA building blocks in the PDGFRA gene (point mutations) can also cause this condition, although these mutations are seen very rarely.

The protein produced from the FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) has the function of the PDGFRA protein. However, unlike the normal PDGFRA protein, the fusion protein does not require binding of the platelet-derived growth factor protein to be activated. Similarly, point mutations in the PDGFRA gene can result in a PDGFRA protein that is activated without ligand binding. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA fusion gene mutation or point mutations in the PDGFRA gene occur in early blood cells, the growth of eosinophils (and occasionally other blood cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.

Mutations in the PDGFRA gene are associated with gastrointestinal stromal tumors (GISTs). GISTs are a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. The majority of GISTs associated with a mutation in the PDGFRA gene occur in the stomach. In most cases, the genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations, which lead to sporadic GISTs, are present only in the tumor cells and are not inherited. Less commonly, PDGFRA gene mutations that increase the risk of developing GISTs are inherited from a parent, which can lead to familial GISTs.

PDGFRA gene mutations associated with GISTs create a protein that no longer requires binding of the platelet-derived growth factor protein to be activated. As a result, the PDGFRA protein and the signaling pathways are constitutively activated, which increases cell proliferation and survival, leading to tumor formation.

PDGFRA gene mutations that lead to a constitutively active PDGFRA protein are also associated with inflammatory fibroid polyps, which are small, noncancerous (benign) tumors that form in the gastrointestinal tract. These tumors are made up of fibrous tissue and usually contain cells known to cause inflammation (inflammatory cells). As in GISTs, the constitutively active PDGFRA protein leads to the overgrowth of cells and formation of tumors.

Bi-directional sequencing of exons 12 and 18 of the PDGFRA (platelet-derived growth factor alpha) gene. These exons are mutation hotspots that account for the majority of PDGFRA mutations detected in gastrointestinal stromal tumors (GISTs) including the common TKI-resistance mutation D842V. Solid tumor enrichment is performed before extraction.

PDGFRA Amplification by FISH is available for detection of PDGFRA amplifications, which occur in approximately 30% of pediatric and 20% of adult high-grade astrocytomas, and may have prognostic and/or therapeutic implications.

PDGFRA Rearrangement by FISH is also available for detection of FIP1L1-PDGFRA fusion, which may be found in myeloid/lymphoid neoplasms with eosinophilia. Bone marrow and peripheral blood are acceptable specimens.

PDGFRa mutations are found in soft-tissue sarcomas including gastrointestinal stromal tumors (GISTs). Identification of mutations is informative for sensitivity or resistance to tyrosine kinase inhibitor (TKI) therapy.

*The CPT codes provided with our test descriptions are based on AMA guidelines and are for informational purposes only. Correct CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.

The FIP1L1-PDGFR Gene Rearrangement Test is a specialized genetic test that helps in diagnosing and managing a group of rare blood disorders known as hypereosinophilic syndromes (HES). HES encompasses conditions characterized by an abnormally high number of eosinophils, a type of white blood cell, in the blood or tissues. The FIP1L1-PDGFR gene rearrangement is a specific chromosomal abnormality found in a subset of patients with HES. This abnormality involves the fusion of the FIP1L1 gene and the PDGFR-alpha gene, resulting in a mutated gene that leads to uncontrolled cell growth.

HES can cause a range of symptoms and complications as eosinophils can affect various organs, including the heart, lungs, and skin. The detection of the FIP1L1-PDGFR gene rearrangement has significant implications for the management and treatment of HES, as patients with this mutation respond well to specific targeted therapies, such as imatinib.

The FIP1L1-PDGFR Gene Rearrangement Test is a laboratory test used to detect the presence of a specific genetic mutation where parts of the FIP1L1 and PDGFR-alpha genes are fused. This mutation is associated with certain types of hypereosinophilic syndromes (HES).

This test is important because identifying the FIP1L1-PDGFR gene rearrangement can help in diagnosing certain forms of HES. Additionally, it helps in determining the appropriate treatment, as patients with this gene rearrangement respond well to targeted therapies like imatinib.

The sample is usually collected from blood or bone marrow. A healthcare professional will draw blood from a vein, usually in your arm. In some cases, a bone marrow sample might be taken from the hip bone.

The FIP1L1-PDGFR Gene Rearrangement Test is an invaluable diagnostic tool in the management of hypereosinophilic syndromes. The identification of this gene rearrangement guides treatment decisions and can significantly impact the course of the disease. If you or a family member are experiencing symptoms or have been diagnosed with HES, consulting your doctor about the potential benefits of this test is crucial. Through informed medical care, individuals with HES can lead a productive life while managing the condition effectively.

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Prostate cancer (PC) is the most frequent malignancy in men1. Despite a relatively low mortality rate, the sheer PC incidence rate makes it the second most common cause of male cancer death in developed countries. Differentiation between patients with an aggressive and potentially deadly form of PC versus patients with indolent disease remains a challenge. Contemporary risk stratification leads to a significant overtreatment (radical therapy), but possibly also an undertreatment of some patients2,3,4. There is a definite need for better prognostic tools to aid in the prediction of which patients will benefit from curative treatment.

The platelet derived growth factor ligands (PDGFs) and their receptors (PDGFRs) have emerged as key regulators of cell growth and division, and mediate significant impact on malignant cells and the tumor microenvironment5. As potent mitogens for cells of mesenchymal origin, the PDGFs are important regulatory proteins for fibroblasts, smooth muscle cells and glial cells. They are involved in embryonic development, cell proliferation, cell migration and stimulate wound healing in the adult6. In particular, these factors play a significant role in angiogenesis in which mutational activation or upregulation of the PDGFs or PDGFRs may lead to uncontrolled blood vessel formation and cancer.

Although several PDGFR inhibitors are approved for clinical use in other cancer types, attempts at PDGFR inhibition in PC patients have so far been unsuccessful with no improvement in disease specific survival, despite robust pre-clinical results8,9,10.

Alternations of PDGFRs have been detected in several cancers including pancreatic, ovarian, breast, gastric, thymoma, gastrointestinal stromal tumor, osteosarcoma, hepatocellular and hematologic cancers among others11,12,13,14,15. In PC, PDGF-D seems to be involved in osteoclastic differentiation and establishment of bone metastasis16. High levels of PDGFR-β in PC tumor stroma and non-malignant prostate tissue have been associated with shorter cancer specific survival for PC patients17. However, PDGFR-β expression for PC patients with a localized disease and its prognostic value post radical treatment has, to our knowledge, not been previously examined.

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