title: Detection of Novel t(12;17)(p12;p13) in Relapsed Refractory Acute Myeloid Leukemia by Anchored Multiplex PCR(AMP)-based Next-Generation Sequencing.
abstract: Although several technologies can be used to detect gene fusions, anchored multiplex PCR next-generation sequencing (AMP-NGS) offers the advantage of novel fusion detection and the ability to multiplex multitudinous genes. We applied AMP-NGS technology in the evaluation of a 56-year-old gentleman with myelodysplastic syndrome transformed acute myeloid leukemia (AML). Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy. At progression patients had normal cytogenetics but NGS profiling showed ETV6 c.416_417del CT frame shift and U2AF1 S34F mutations. Patient attains brief remission of 2 months after induction chemotherapy and then he was refractory to 2 salvage chemotherapy regimens. Reassessment after failing second salvage, identified t(12;17)(p13;p13)[20] by karyotype. It was postulated that the 12p13 locus might represent a new rearrangement of ETV6. AMP-NGS confirmed involvement of the ETV6 with discovery of a novel fusion partner, HIC1. The detection of the novel fusion partners was supported by the breakpoints originally observed by karyotype. This discovery of ETV6-HIC1 gene fusion by AMP-NGS technology provided new insight into a leukemogenic pathway in AML. Future use of this technology can serve as an adjunct tool in workup of patients with AML and can also help in formulating therapeutic strategies.
authors.affiliation: Department of Internal Medicine, Brandon Regional Hospital, Brandon.
authors.forename: Talha
authors.initials: T
authors.lastname: Badar
authors.affiliation: ArcherDx, Boulder, CO.
authors.forename: Laura
authors.initials: L
authors.lastname: Johnson
authors.affiliation: ArcherDx, Boulder, CO.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Trifilo
authors.affiliation: ArcherDx, Boulder, CO.
authors.forename: Helen
authors.initials: H
authors.lastname: Wang
authors.affiliation: ArcherDx, Boulder, CO.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kudlow
authors.affiliation: Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, FL.
authors.forename: Eric
authors.initials: E
authors.lastname: Padron
authors.affiliation: Labcorp, Durham, NC.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Pappenhausen
authors.affiliation: Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, FL.
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hussaini
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D051741:Kruppel-Like Transcription Factors; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C499808:HIC1 protein, human