PPP1R7 Is a Novel Translocation Partner of CBFB via t(2;16)(q37;q22) in Acute Myeloid Leukemia.

In a subset of acute myeloid leukemia (AML) cases, the core binding factor beta subunit gene ( CBFB ) was rearranged via inv(16)(p13.1q22) or t(16;16)(p13.1;q22), in which the smooth muscle myosin heavy chain 11 gene ( MYH11 ) was the partner ( CBFB::MYH11 ). Rare variants of CBFB rearrangement occurring via non-classic chromosomal aberrations have been reported, such as t(1;16), t(2;16), t(3;16), t(5;16), and t(16;19), but the partners of CBFB have not been characterized. We report a case of AML with a complex karyotype, including t(2;16)(q37;q22), in which the protein phosphatase 1 regulatory subunit 7 gene ( PPP1R7 ) at chromosome 2q37 was rearranged with CBFB ( CBFB::PPP1R7 ). This abnormality was inconspicuous by conventional karyotype and interphase fluorescence in situ hybridization (FISH), thus leading to an initial interpretation of inv(16)(p13.1q22); however, metaphase FISH showed that the CBFB rearrangement involved chromosome 2. Using whole genome and Sanger sequencing, the breakpoints were identified as being located in intron 5 of CBFB and intron 7 of PPP1R7 . A microhomology of CAG was found in the break and reconnection sites of CBFB and PPP1R7 , thus supporting the formation of CBFB::PPP1R7 by microhomology-mediated end joining.