title: A new complex rearrangement involving the ETV6, LOC115548, and MN1 genes in a case of acute myeloid leukemia.
abstract: A new complex rearrangement involving chromosome bands 5q13, 12p13, 22q11, and 3q12 was identified and characterized in a patient with acute myeloid leukemia. Fluorescence in situ hybridization showed the involvement of the ETV6 gene in 12p13. ETV6 primers were specifically designed for 3'- and 5'-RACE-PCR experiments, which led to the identification of the other two rearranged genes. The derivative chromosome 5 harbored a fusion of the ETV6 sequence with that of the LOC115548 gene. The two genes were placed in opposite orientation and did not encode a fusion protein. On the derivative chromosome 12, ETV6 was fused to the MN1 gene on chromosome 22. Also in this case, the insertion, within the MN1 sequence, of a portion of chromosome 3 prevented the formation of a fusion protein. Finally, the derivative chromosome 22 contained the 3' portions of both LOC115548 and MN1, and no fusion transcript with coding potential could be predicted. In conclusion, all chromosome breakpoints led to the truncation of the three involved genes in the absence of predicted fusion proteins. This study lends further support to the hypothesis that gene disruption resulting in either loss of function or haploinsufficiency may be relevant in acute myeloid leukemia pathogenesis.
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. belloni@ifom-firc.it
authors.forename: Elena
authors.initials: E
authors.lastname: Belloni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trubia
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Valentina
authors.initials: V
authors.lastname: Derme
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccioni
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D002892:Chromosomes, Human, Pair 22 / Q000648:ultrastructure; D002893:Chromosomes, Human, Pair 3 / Q000648:ultrastructure; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein