Development of an ATM mutation during disease progression. The ATM mutation 4393 insertion A was not present at the time of diagnosis of CLL in 1985 (bottom sequence) but was present in tumor material from 1994, after treatment with chlorambucil (top sequence). After the insertion of an additional adenine (A) nucleotide in one allele, the reading frames of the 2 alleles become out of line, resulting in a double sequence; one corresponding to the mutated and one corresponding to the unmutated allele.