75. Novel complex translocation involving PDGFRA::PRKG2, in a myeloid neoplasm with basophilia sample by OGM

Aly Abdelkareem

Alex Hastie

Dr. Alex Hastie is the Vice President of Clinical and Scientific Affairs at Bionano Laboratories and has spent over a decade of his career focusing on the development, implementation, and various clinical and translational research applications of optical genome mapping (OGM).  Dr. Hastie is an active contributor to the Human Genome Structural Variation Consortium (HGSV) and other genome consortia (T2T, NIST, Human Pangenome Project, etc.). Dr. Hastie has authored over 55 publications including multiple benchmarking studies and applications of OGM to disease.  Prior to Bionano Laboratories, Dr Hastie worked as a post doctoral fellow at Max Planck Institute. Dr. Hastie worked on protein-protein interactions during his doctoral thesis work conducted at Roswell Park Cancer Institute. Dr Hastie is a member of multiple professional societies such as AACR, ACMG, AMP, ASHG, and CGC and has collaborated with scientists around the world that have resulted in dozens of publications on optical genome mapping in clinical and translational research.


Alex Hastiea, Sandeep Raob, Shruthi Neelamegamb, Trilochan Sahooa, Alka Chaubeya, Sachin Jadhavb

aBionano Labortories, San Diego, CA, United States; bHCG Group of Hospitals, Bengaluru, Karnataka, India

Myeloproliferative neoplasms are often characterized by genetic abnormalities which activate requested new titletyrosine kinases resulting in uncontrolled cell proliferation. Conventional cytogenetic techniques are used to identify these abnormalities but they have low resolution and/or are targeted in nature among other limitations. Optical genome mapping (OGM) overcomes these limitations, providing better detection of structural rearrangements of known clinical relevance. A case where multiple rearrangements which were identified via OGM, leading to a targeted  therapy will be presented.

This case initially presented with palm swelling/itching, significant weight loss, fever/chills, persistent nausea/vomiting. Bone marrow aspirate and biopsy and flow cytometry found an increase in myeloid blasts, eosinophils, and basophils.

OGM revealed a more complete and higher resolution description of these structural variants:: ogm[GRCh38] (X)x1~2,inv(4)(q12q21.21)(54281141_81170345),t(4;11)(q12;p15.4)(54269171;8150536), t(4;17)(q21.21;q22)(81167017;55043518),8p23.3q22.3(61805_107404418)x2~3,t(8;11)(q23.1;p15.4)(107507607;8159472),t(8;17)(q23.1;q22)(107496941;55048499),17q22q25.3(55115496_83246392)x2~3,(21)x2~3

A 5-break unbalanced rearrangement between chromosomes 4, 8, 11, and 17 caused fusion of several genes, most importantly, PDGFRA::PRKG2. PDGFRA::PRKG2 fusion is rare but has been observed in a case of myeloproliferative neoplasm with basophilia (PMID:35342043). Identification of this fusion, undetected via karyotype, led to a final diagnosis for the patient of myeloid neoplasm with tyrosine kinase gene fusion in accelerated phase with hyperbasophilia. This case demonstrates the utility of OGM providing precise information about complex genomic aberrations that are diagnostic and prognostic for a heme malignancy.