title: Molecular analysis of a new variant of the CBF beta-MYH11 gene fusion.
abstract: The inv(16)(p13q22) is observed in 16% of patients with acute myelogenous leukemia (AML). It is classically found in the AML M4Eo subtype, which has distinctive morphological abnormalities in the bone marrow including myelomonocytic differentiation and an increase in atypical bone marrow eosinophils. A gene fusion involving CBFbeta and MYH11 is invariably created by the inv(16)(p13q22) and is thought to be a necessary genetic lesion in this form of leukemia. The most common fusion point occurs at CBFbeta nucleotide (nt) 495 and MYH11 nt 1921; however, several rare variants have been described. We report a patient with AML M4Eo whose leukemic cells contained two distinct CBFbeta-MYH11 transcripts, one rare and the other previously undescribed. Both gene fusion products were cloned and sequenced and the breakpoints were identified. These were at CBFbeta nt 495 and MYH11 nt 994 and CBFbeta nt486 and MYH11 nt 1591. The CBFbeta(495)/MYH11(994) fusion is seen in 5-7% of AML M4Eo, while the CBFbeta(486)/MYH11(1591) fusion is novel. We postulate that these two fusions arose from a single rearranged chromosome 16 by way of alternative splicing. These fusions were associated with a good prognosis in this patient. Molecular diagnostic facilities should be aware of the existence of the CBFbeta(486)/MYH11(1591) variant and its potential association with the previously described type E fusion.
authors.affiliation: Department of Cellular and Molecular Biology, Ontario Cancer Institute, Toronto, Ont., Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stulberg
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Kathy
authors.initials: K
authors.lastname: Chun
authors.forename: Jason
authors.initials: J
authors.lastname: Tokunaga
authors.forename: Richard A
authors.initials: RA
authors.lastname: Wells
mesh_terms: D000368:Aged; D017398:Alternative Splicing; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16; D004252:DNA Mutational Analysis; D005260:Female; D015321:Gene Rearrangement; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm