Proviral insertions in accelerated tumors of

E2A-PBX1 mice frequently target theNotch1 gene with a predilection for its 3′ exonic sequences. (A) Southern blot analyses of tumor DNAs using probes specific for cluster regions I (left panel) or II (right panel) in theNotch1 gene. Analysis for cluster region I used aNotch1 cDNA fragment spanning nucleotides 3851-4861 onEcoRV-digested DNA. Rearrangements affecting cluster region II were detected with a 0.9-kb fragment of Notch1 cDNA (nucleotides 7053-7957) on DNA digested with KpnI. Dashes indicate migrations of germline Notch1 DNA fragments. All other bands correspond to clonally rearranged Notch1 genes. (B) Nucleotide sequences are shown for junctions of LTR and genomic DNA at proviral integration sites in tumors. Sequences homologous to the U5 portion of the 3′ LTR are underlined; Notch1 exonic sequences are in bold and numbers indicate corresponding nucleotide position of the Notch1 open reading frame. Nucleotide insertions observed in 2 of the cases are shown in lower case.