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), ref ractory anemia with excess of blasts. He had received chemotherapy with teg afur 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 i n 13 and 7 cells, respectively. Fluorescence in situ hybridization (FISH) a nalysis with chromosome-specific DNAs revealed that these alterations origi nated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q1 3), 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), respe ctively. 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;1 2)(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), an d that the interstitial deletion (12)(p11p13) occurred following t(5;12) du ring clonal evolution. del(12)(p11p13, including the rearranged ETV6 gene, may be implicated in the progression of MDS. (C) 2000 Elsevier Science Inc. All rights reserved.