RUNX1 truncation resulting from a cryptic and novel t(6;21)(q25;q22) chromosome translocation in acute myeloid leukemia: A case report.
Fluorescence in situ hybridization examination of a pediatric AML patient whose bone marrow cells carried trisomy 4 and FLT3-ITD mutation, demonstrated that part of the RUNX1 probe had unexpectedly moved to chromosome band 6q25 indicating a cryptic t(6;21)(q25;q22) translocation. RNA sequencing showed fusion of exon 7 of RUNX1 with an intergenic sequence of 6q25 close to the MIR1202 locus, something that was verified by RT-PCR together with Sanger sequencing. The RUNX1 fusion transcript encodes a truncated protein containing the Runt homology domain responsible for both heterodimerization with CBFB and DNA binding, but lacking the proline-, serine-, and threonine-rich (PST) region which is the transcription activation domain at the C terminal end. Which genetic event (+4, FLT3-ITD, t(6;21)-RUNX1 truncation or other, undetected acquired changes) was more pathogenetically important in the present case of AML, remains unknown. The case illustrates that submicroscopic chromosomal rearrangements may accompany visible numerical changes and perhaps should be actively looked for whenever a single trisomy is found. An active search for them may provide both pathogenetic and prognostic novel information.
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, NO-0424 Oslo, Norway.
Ioannis
I
Panagopoulos
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, NO-0424 Oslo, Norway.
Synne
S
Torkildsen
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, NO-0424 Oslo, Norway.
Ludmila
L
Gorunova
Pediatric Medicine, Oslo University Hospital, NO-0424 Oslo, Norway.
Aina
A
Ulvmoen
Laboratory Medicine Program, Department of Haematopathology, University Health Network, Toronto, Ontario M5G 2C4, Canada.
Anne
A
Tierens
Pediatric Medicine, Oslo University Hospital, NO-0424 Oslo, Norway.
Bernward
B
Zeller
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, NO-0424 Oslo, Norway.
Sverre
S
Heim
D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic / Q000235:genetics*
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C493728:RUNX1 protein, human
Leukemia. 2012 Feb;26(2):265-70
21869842
Future Oncol. 2011 Jan;7(1):77-91
21174539
Oncogene. 2004 May 24;23(24):4284-96
15156185
Arch Pathol Lab Med. 2011 Nov;135(11):1504-9
22032582
Genes Chromosomes Cancer. 2005 Nov;44(3):265-70
16015645
Cancer Genet Cytogenet. 2010 Oct 15;202(2):94-100
20875871
J Clin Oncol. 2012 Sep 1;30(25):3109-18
22753902
Cell Growth Differ. 1997 Mar;8(3):319-26
9056674
Haematologica. 2012 Nov;97(11):1743-50
22580999
Blood. 2013 Mar 21;121(12):2213-23
23321257
Cancer Genet. 2012 Jul-Aug;205(7-8):365-72
22867997
Blood. 2001 Apr 1;97(7):2168-70
11264187
Oncogene. 2015 Sep 10;34(37):4845-54
25500544
Blood. 2013 Apr 11;121(15):2882-90
23372166
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7784-8
8395054
J Clin Oncol. 2015 Dec 20;33(36):4247-58
26573082
Blood. 2012 Aug 2;120(5):978-84
22730539
Korean J Intern Med. 2003 Mar;18(1):13-20
12760263
Oncogene. 2016 Jan 7;35(1):125-34
25798834
Blood. 2011 Feb 24;117(8):2348-57
21148331
Leukemia. 2006 Jun;20(6):1187-9
16598304
Exp Hematol Oncol. 2014 Mar 19;3:8
24646765
Haematologica. 2007 Aug;92(8):1123-6
17650443
Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1044-8
8577711
Blood. 2009 Oct 1;114(14):3001-7
19666867
Br J Haematol. 2010 Mar;148(6):938-43
20064152
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10431-4
1720541
PLoS Comput Biol. 2011 May;7(5):e1001138
21625565
PLoS Med. 2007 May;4(5):e172
17503961
Blood. 2006 Dec 1;108(12):3654-61
16912228
Blood. 2010 Jan 21;115(3):453-74
19880497
Oncogene. 2008 Apr 3;27(15):2249-56
17968322
Hum Mol Genet. 2010 Mar 15;19(6):1048-57
20035012
Leuk Res. 2003 Nov;27(11):983-91
12859991
Genes Chromosomes Cancer. 2013 Dec;52(12):1114-22
24123676
Oncol Rep. 2013 Oct;30(4):1549-52
23877199
Blood. 2008 Apr 15;111(8):4297-308
18192504
Genes Chromosomes Cancer. 2009 Dec;48(12):1027-36
19760607
EMBO J. 1995 Jan 16;14(2):341-50
7530657
Leukemia. 2009 Apr;23(4):739-45
19151769
Blood. 2004 Mar 15;103(6):2316-24
14615365
Cancer Genet. 2012 Nov;205(11):608-11
23102734
Blood. 2003 Oct 1;102(7):2387-94
12816873
Genes Chromosomes Cancer. 2006 Nov;45(11):1072-6
16900497
Genes Chromosomes Cancer. 2007 Jul;46(7):635-43
17394134
Leukemia. 2006 Feb;20(2):224-9
16357831
Am J Hematol. 2014 Nov;89(11):1063-81
25318680
Blood. 2007 Aug 15;110(4):1308-16
17485549
Genes Chromosomes Cancer. 2004 Feb;39(2):110-8
14695990
Leukemia. 2003 Aug;17(8):1665-6
12886257
Oncogene. 2008 Aug 21;27(36):4933-42
18469864
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6859-63
8341710
Hematology Am Soc Hematol Educ Program. 2013;2013:220-6
24319184
Nucleic Acids Res. 1995 Jul 25;23(14):2762-9
7651838
PLoS One. 2010 Jun 25;5(6):e11318
20593002
Leukemia. 2013 Sep;27(9):1891-901
23783394