Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene.
We report here a 65-year-old man with a myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. He had received chemotherapy with tegafur for renal carcinoma. Chromosome analysis of bone marrow cells revealed complex karyotypes; del(5)(q13) was observed in all 20 metaphase spreads, and two related aberrations, add(12)(p11) and add(12)(p13), were detected in 13 and 7 cells, respectively. Fluorescence in situ hybridization (FISH) analysis with chromosome-specific DNAs revealed that these alterations originated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q13), add(12)(p11), and add(12)(p13) were revised as der(5)t(5;12)(q13;p13), der(12)del(12)(p11p13)t(5;12)(q13;p13), and der(12)t(5;12)(q13;p13), respectively. Fluorescence in situ hybridization with a series of cosmid probes spanning the ETV6 gene showed that the 12p13 breakpoint on the der(12)t(5;12)(q13;p13) was located in intron 1, but the exon 1 signal was deleted. Our results suggest that a fusion gene was generated between the 5'-end of an unidentified partner at 5q13 and the 3'-end of ETV6 by t(5;12)(q13;p13), and that the interstitial deletion (12)(p11p13) occurred following t(5;12) during clonal evolution. del(12)(p11p13), including the rearranged ETV6 gene, may be implicated in the progression of MDS.
Yamamoto
K
K
Department of Hematology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Nagata
K
K
Yagasaki
F
F
Tsurukubo
Y
Y
Tamura
A
A
Taniwaki
M
M
Hamaguchi
H
H
D000368:Aged; D002872:Chromosome Deletion; D020223:Chromosome Painting; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000648:ultrastructure*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000648:ultrastructure*; D002999:Clone Cells / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D017353:Gene Deletion; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein