Identification of a novel translocation t(4;14)(q24;q32) and identification of BANK1 as an IGH-associated partner. (a, left) Karyotype showing the t(4;14)(q23;q32) translocation and trisomy 9. (a, right) Metaphase and interphase FISH assay showing rearrangement of the IGH gene. Fusion (yellow) signal indicates the normal IGH allele and the two arrows show the split signals of IGH on the der(4) and der(14) indicating the rearrangement of the gene. (b) The structures of the germline IGH and BANK1 alleles, as well as the translocated IGH/BANK1 allele in der(14) and der(4), are depicted. Vertical boxes denote exons of the BANK1 gene. Sequence analysis of the breakpoint region showed that the BANK1 gene is juxtaposed to IGH. The breakpoint is located at the switch (S) region proximal to the Cα2 gene segment at the 3′ portion of the IGH gene, and in intron 1 of the BANK1 gene, ∼830 bp telomeric to the 3′ end of exon 1a. IGH and BANK1 are arranged in a head-to-head transcription orientation. This IGH/BANK1 translocation results in removal of the major BANK1 promoter from the rest of the gene. Four neighboring coding genes (PPP3CA, MIR1255A, FLJ20021 and SLC39A8) are shown by horizontal arrows, the direction and length of which represent the orientation and size of the transcription units. The approximate genomic distance between the 5′ or 3′ end of BANK1 and the closest exon of the neighboring genes are indicated. C, constant; cen, centromeric; E, enhancer; S, switch; tel, telomeric. (c) The sequence alignment of the translocation breakpoint is shown. IGH sequence is underlined and BANK1 sequence is in bold. The breakpoint is boxed (the exact nucleotide location cannot be determined). The translocated BANK1 sequence shows a C to G mutation (in italics) in very close vicinity to the breakpoint. (d) Interphase nuclei were hybridized with BAC RP11-96J17 (green, centromeric) and BAC RP11-138I19 (red, telomeric) in 4q24 to confirm BANK1 rearrangement. The arrow indicates the green signal present on derivative chromosome 4 generated by a split within RP11-96J17. The arrowhead points to the signal generated from the remainder of BAC RP11-96J17 and the adjacent RP11-138I19, present on derivative chromosome 14. The yellow signal (not marked) in the cells corresponds to the intact, untranslocated BANK1 allele. Only exons 1a, 1b, 2 and 3 of BANK1 are shown.