Molecular characterisation of a recurrent, semi-cryptic RUNX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukaemia

TY - JOUR

T1 - Molecular characterisation of a recurrent, semi-cryptic RUNX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukaemia

AU - Foster, Nicola

AU - Paulsson, Kajsa

AU - Sales, Mark

AU - Cunningham, Joan

AU - Groves, Michael

AU - O'Connor, Nigel

AU - Begum, Suriya

AU - Stubbs, Tracy

AU - McMullan, Dominic J.

AU - Griffiths, Michael

AU - Pratt, Norman

AU - Tauro, Sudhir

PY - 2010/3

Y1 - 2010/3

N2 - P>A proportion of cytogenetic abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) may escape detection by high-resolution genomic technologies, but can be identified by conventional cytogenetic and molecular analysis. Here, we report the detection of a reciprocal translocation t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH). Reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis identified a fusion between RUNX1 and the gene encoding ubiquitin specific peptidase-42 (USP42), with splice-variants and variable break-points within RUNX1. Combined cytomorphology and FISH studies in MDS marrow revealed abnormal RUNX1 signals within megakaryocytes, suggesting that the acquisition of t(7;21)(p22;q22) does not confer complete differentiation arrest and may represent an early genetic event in leukaemogenesis. Single nucleotide polymorphism-arrays failed to detect additional sub-microscopic genomic changes predisposing to or associated with t(7;21). Molecular analysis of 100 MDS and AML marrow specimens by RT-PCR did not reveal new cases with the RUNX1-USP42 fusion. Thus, our studies have identified t(7;21)(p22;q22) as a rare but recurrent abnormality in MDS/AML, with the existence of alternative spliced forms of the RUNX1-USP42 transcript in different patients. Further studies are required to identify the potential contribution of these splice-variants to disease heterogeneity.

AB - P>A proportion of cytogenetic abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) may escape detection by high-resolution genomic technologies, but can be identified by conventional cytogenetic and molecular analysis. Here, we report the detection of a reciprocal translocation t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH). Reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis identified a fusion between RUNX1 and the gene encoding ubiquitin specific peptidase-42 (USP42), with splice-variants and variable break-points within RUNX1. Combined cytomorphology and FISH studies in MDS marrow revealed abnormal RUNX1 signals within megakaryocytes, suggesting that the acquisition of t(7;21)(p22;q22) does not confer complete differentiation arrest and may represent an early genetic event in leukaemogenesis. Single nucleotide polymorphism-arrays failed to detect additional sub-microscopic genomic changes predisposing to or associated with t(7;21). Molecular analysis of 100 MDS and AML marrow specimens by RT-PCR did not reveal new cases with the RUNX1-USP42 fusion. Thus, our studies have identified t(7;21)(p22;q22) as a rare but recurrent abnormality in MDS/AML, with the existence of alternative spliced forms of the RUNX1-USP42 transcript in different patients. Further studies are required to identify the potential contribution of these splice-variants to disease heterogeneity.

KW - RUNX1-USP42

KW - acute myeloid leukaemia

KW - myelodysplastic syndrome

KW - T(8/21)

KW - MUTATIONS

KW - FUSION

KW - AML1

U2 - 10.1111/j.1365-2141.2009.08039.x

DO - 10.1111/j.1365-2141.2009.08039.x

M3 - Article

C2 - 20064152

SN - 0007-1048

VL - 148

SP - 938

EP - 943

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 6

ER -