Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping

TEL/ETV6 is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners; 35 different chromosome bands have been involved in ETV6 translocations, of which 13 have been cloned. To identify additional ETV6 partner genes and to characterize the chromosomal abnormali ties more fully, Lye studied bone marrow samples from patients known to hav e rearrangements of 12p, using fluorescence in situ hybridization (FISH) an d spectral karyotyping (SKY). FISH analysis was done with 14 probes located on 12p12.1 to 12p13.3. Nine ETV6 rearrangements were identified using FISH . The aberrations include t(1;12)(p36;p13), t(4;12)(q12;p13) (two patients) , t(4;12)(q22;p13), t(6;12)(p21;p13), der(6)t(6;21)(q15;q?)t(12;21)(p13;q22 ), t(6;12)(q25;p13). inv(12)(p13q24), and t(2;2;5;12;17)(p25;q23;q31;p13;q1 2), Six new ETV6 partner bands were identified: 1p36, 4q22, 6p21, 6q25, 12q 24, and 17q12. Our present data as well as previous data from us and from o ther researchers suggest that ETV6 is involved in 41 translocations. The br eakpoints in ETV6 were upstream from the exons coding for the HLH (helix-lo op-helix) domain in six cases. Although cytogenetic analysis identified 12p abnormalities in all cases, FISH and SKY detected new and unexpected chrom osomal rearrangements in many of them. Thus, complete characterization of t he samples was achieved by using all three techniques in combination, (C) 2 001 Wiley-Liss, Inc.