Analysis of ATM mutations. (A) Exon skipping in patient “Dia”. Upper panel, normal partial cDNA sequence demonstrated in the “Dia” EBV cell line sample as compared with the tumor cDNA sequence, which is deleted for the 105-bp of exon 46. Lower panel, genomic sequence of germline (EBV) and tumor (T-PLL) DNAs. Exon 46 sequence is indicated in bold. The G>A mutation is double underlined. (B) Insertion of 29 nt in tumor DNA from patient “Bat”. Tumor cDNA sequences contained, in approximately equal amounts, wild-type and mutated (4182ins29) sequences. The normal corresponding peptide sequence is indicated. The stop codon due to the frameshift as a consequence of the 29 nt insertion is indicated in bold and underlined. Lines indicated the correspondence between the mutated cDNA sequence and the normal published genomic sequence (accession number U82828). The genomic sequence of “Bat” tumor DNA was identical to the published one. The putative splice donor and acceptor sites on each side of the 29 nt insertion are doubly underlined, and the exon 29 sequence is indicated in bold. Numbering of nucleotides is based on either the ATM transcript sequence (accession number U33841) for the cDNA, or on the full-length ATM gene sequence (accession number U82828) for the genomic DNA.25,32Numbering of codons starts at the initiating ATG.