FLUORESCENCE IN-SITU HYBRIDIZATION ANALYSES OF HEMATOLOGIC MALIGNANCIES REVEAL FREQUENT CYTOGENETICALLY UNRECOGNIZED 12P REARRANGEMENTS

Thirty-two hematologic malignancies - nine with cytogenetically identi fied 12p abnormalities and 23 with whole or partial losses of chromoso me 12 - were selected for fluorescence in situ hybridization (FISH) in vestigations of 12p. These analyses revealed structural 12p changes, s uch as translocations, deletions, insertions, inversions and amplifica tion, in 20 cases. ETV6 rearrangements were detected in three acute le ukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as t he sole anomaly. The second case, an acute myeloid leukemia (AML), dis played complex abnormalities involving, among others, chromosomes 9 an d 12. The third case, also an AML, had an Insertion of the distal part of EPV6 into chromosome arm 11q and into multiple ring chromosomes, w hich also contained chromosome 11 material, resulting in an amplificat ion of a possible fusion gene. The fusion partners in these cases rema in to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to r esult in interchromosomal rearrangements, possibly indicating the loca tion of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or i nterstitial 12p deletions in 18 cases, Seven myeloid malignancies show ed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported lo be frequently lost in leukemias. In four cases, t he deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indic ating a region of deletion not including this gene. However, one myelo dysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 a nd CDKN1B genes.