Breakpoints of PTEN microdeletions. (A) Schematic representation of the PTEN gene. Missense mutations are represented by open triangles above the exons, whereas a silent mutation is presented as a filled gray triangle as shown before.18 Nonsense insertion/deletion mutations are indicated by a filled black triangle. Left- or right-pointing open triangles in introns 1, 3, and 5 represent cRSSs. (B) Sequences of cloned intron 1-3 type I and type II breakpoints and the intron 3-5 type III breakpoint for T-ALL patients with PTEN microdeletions. cRSSs are indicated by a box with the canonic CAC trinucleotide sequences or the corresponding GTG nucleotides in heptamer sequences indicated in bold and underlined. Insertion of non-template, random nucleotides are shown in bold. (C) Examples of sequence traces of cDNA resulting from type I, II, and III microdeletions. (D) Involvement of specific cRSSs in illegitimate RAG-mediated recombination events resulting in types I and II microdeletions (signal joint) and aberrant PTEN splice variant or the type III with the aberrant exon 4-5 microdeletion PTEN transcript (coding joint).
