{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T19:20:46Z","timestamp":1696360846867},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,9,29]],"date-time":"2010-09-29T00:00:00Z","timestamp":1285718400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Abnormalities of 11q23 involving the <jats:italic>MLL<\/jats:italic> gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel <jats:italic>MLL<\/jats:italic> fusion partner in a pediatric patient with <jats:italic>de novo<\/jats:italic> biphenotypic acute leukemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the <jats:italic>CT45A2<\/jats:italic> gene as novel <jats:italic>MLL<\/jats:italic> fusion partner in pediatric acute leukemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Fluorescence <jats:italic>in situ<\/jats:italic> hybridization of bone marrow G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the <jats:italic>MLL<\/jats:italic> gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing <jats:italic>MLL<\/jats:italic> exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the <jats:italic>CT45A2<\/jats:italic> gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the <jats:italic>DDX26B<\/jats:italic> gene (exons 9-16) and the entire <jats:italic>CT45A1<\/jats:italic> gene was identified. RNA analysis revealed the presence of a novel <jats:italic>MLL-CT45A2<\/jats:italic> fusion transcript in which the first 9 exons of the <jats:italic>MLL<\/jats:italic> gene were fused in-frame to exon 2 of the <jats:italic>CT45A2<\/jats:italic> gene, resulting in a spliced <jats:italic>MLL<\/jats:italic> fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE\/L1 and SINE\/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We have identified <jats:italic>CT45A2<\/jats:italic> as a novel spliced <jats:italic>MLL<\/jats:italic> fusion partner in a pediatric patient with <jats:italic>de novo<\/jats:italic> biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since <jats:italic>CT45A2<\/jats:italic> is the first Cancer\/Testis antigen family gene found fused with <jats:italic>MLL<\/jats:italic> in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-10-518","type":"journal-article","created":{"date-parts":[[2010,9,29]],"date-time":"2010-09-29T18:14:58Z","timestamp":1285784098000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel spliced fusion of MLL with CT45A2in a pediatric biphenotypic acute leukemia"],"prefix":"10.1186","volume":"10","author":[{"given":"Nuno","family":"Cerveira","sequence":"first","affiliation":[]},{"given":"Claus","family":"Meyer","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Lurdes","family":"Torres","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Lisboa","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Bizarro","sequence":"additional","affiliation":[]},{"given":"Cec\u00edlia","family":"Correia","sequence":"additional","affiliation":[]},{"given":"Luc\u00edlia","family":"Norton","sequence":"additional","affiliation":[]},{"given":"Rolf","family":"Marschalek","sequence":"additional","affiliation":[]},{"given":"Manuel R","family":"Teixeira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,9,29]]},"reference":[{"key":"2317_CR1","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"SH Swerdlow","year":"2008","unstructured":"Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW: WHO classification of tumours of haematopoietic and lymphoid tissues. 2008, Lyon: IARC"},{"key":"2317_CR2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.semcancer.2005.01.007","volume":"15","author":"A Daser","year":"2005","unstructured":"Daser A, Rabbitts TH: The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. 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