HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement: Difference between revisions

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Christopher Sullivan, MD, MPH and Daynna J. Wolff, PhD

==WHO Classification of Disease==

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|Acceptable

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|Not Recommended

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* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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|<span class="blue-text">EXAMPLE:</span>

!Chromosomal Pattern

!Molecular Pathogenesis

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|<span class="blue-text">EXAMPLE:</span>

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t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.

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|<span class="blue-text">EXAMPLE:</span>''EGFR''

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins<ref>Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.</ref>.

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PDGFRB encodes a plasma membrane-spanning receptor with five extracellular immunoglobulin-like loops for ligand binding and a split intracellular tyrosine kinase domain. Signal transduction is very similar, with ligand binding inducing dimerization and autophosphorylation of the tyrosine kinase. In addition to its role in embryonic development, PDGFRB mediates chemotactic responses of monocytes, macrophages, and platelets to inflammatory processes. Overexpression has been implicated in solid tumors, such as medulloblastoma and chordoma<ref>Chang, C. C., & Ohgami, R. S. (Eds.). (2018). ''Precision molecular pathology of myeloid neoplasms''. Springer.</ref>.

==Genetic Diagnostic Testing Methods==

==Familial Forms==

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==Notes==

          

<nowiki>*</nowiki>''Citation of this Page'': “Myeloid/lymphoid neoplasm with PDGFRB rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRB_rearrangement</nowiki>.