Supporting Information

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Supporting Figure 2
Supporting Figure 3
Supporting Table 3
Supporting Table 4
Supporting Table 5
Supporting Table 6
Supporting Table 7
Supporting Table 8
Supporting Table 9
Supporting Table 10
Supporting Figure 4
Supporting Figure 5
Supporting Figure 6
Supporting Figure 7
Supporting Figure 8
Supporting Figure 9




Supporting Figure 2

Fig. 2. Detection of mutations using the two-color loss-of-signal assay. Fluorescein-labeled wild-type reference and biotinylated test (sample 968) targets were cohybridized to ATM sense and antisense microarrays. To correct for reproducible differences in the hybridization efficiencies of reference and test targets, the ratio of reference to test target signal at each wild-type perfect-match probe was normalized against ratios derived from separate chip cohybridization experiments. Average sense and antisense strand ratios are plotted on the y axis against the nucleotide position of the corresponding perfect match probe on the x axis. The identity of each exon is listed between the vertical lines depicting their boundaries in the ATM transcript. Peaks corresponding to the sequence-verified 2572 T/C (F858L), 3161 C/G (P1054R), 8451 T/G (Y2817X), and 9022 C/T (R3008C) single-base substitutions are labeled. Variation in the PCR efficiency of exon 8 across all samples resulted in substantial baseline fluctuation, such as the case here, and thus this ATM exon was sequenced for every sample in this study.

Supporting Figure 3

Fig. 3. Distribution of ATM sequence variants in mantle cell lymphoma (MCL). Vertical lines show the boundaries of the 62 coding exons within the ATM transcript. The spacing between these lines is proportional to the size of each exon. Black, gray, and white circles above each exon indicate the presence of deleterious mutations, unclassified missense changes, and neutral variants, respectively. The location of the PI-3 kinase homology domain is provided under the appropriate exons.

Supporting Figure 4

Fig. 4. Correlation of ATM mutation status and genomic deletion status with the proliferation average values from Table 4. The term "aberration" refers to cases with a mutation and/or genomic deletion in the ATM gene. (Upper) Samples are marked green (wild type for indicated abnormality in the ATM gene), red (containing indicated abnormality in the ATM gene), or gray (no data available). They are sorted from right to left according to their relative proliferation values over a 4-fold range.

Supporting Figure 5

Fig. 5. Correlation of p53 mutation status and genomic deletion status with the proliferation average values from Table 7. The term "aberration" refers to cases with a mutation and/or genomic deletion in the p53 gene. (Upper) Samples are marked green (wild type for indicated abnormality in the p53 gene), red (containing indicated abnormality in the p53 gene), or gray (no data available). They are sorted from right to left according to their relative proliferation values over a 4-fold range.

Supporting Figure 6

Fig. 6. Relative expression levels of differentially expressed genes among MCL cases with ATM aberrations relative to those with wild-type alleles. Cases with ATM mutations (A) or genomic deletions (B) are marked. In A and B, the color scale depicts expression levels over a >4-fold range [i.e., lowest (green = -1.70 fold change) to highest (red = 2.64 fold change)] for the indicated genes.

Supporting Figure 7

Fig. 7. Distribution of differentially expressed genes in cases with ATM aberrations. The proportion of differentially expressed genes on each chromosome in (A) ATM mutated (red bars) or (B) ATM deleted (red bars) cases was compared with the proportion of genes on the entire microarray (blue bars) with a c² goodness-of-fit test. The goodness-of-fit tests indicate that differentially expressed genes between cases with ATM deletions and wild-type cases are nonrandomly distributed among the chromosomes. The chromosomal location was unknown for 35% of the genes on the microarray. All clones were included in the analysis, including those on the lists of differentially expressed genes.

Supporting Figure 8

Fig. 8. Relative expression levels of differentially expressed genes among MCL cases with p53 aberrations relative to those with wild-type alleles. Cases with p53 mutations (A) or genomic deletions (B) are marked. The color scale depicts expression levels over a >5-fold range [i.e., lowest (green = -3.5-fold change) to highest (red = 3.6-fold change)] for the indicated genes.

Supporting Figure 9

Fig. 9. Distribution of differentially expressed genes in cases with p53 aberrations. The proportion of differentially expressed genes on each chromosome in (A) p53 mutated (red bars) and (B) p53 deleted (red bars) cases was compared with the proportion of genes on the entire microarray (blue bars) with a c² goodness-of-fit test. The goodness-of-fit tests indicate that differentially expressed genes between cases with p53 deletions and wild-type cases are nonrandomly distributed among the chromosomes. The chromosomal location was unknown for 35% of the genes on the microarray. All clones were included in the analysis, including those on the lists of differentially expressed genes.

Table 3. Deleterious ATM mutations detected

*Data from ref. 1.

1. Fang, N. Y., Greiner, T. C., Weisenburger, D. D., Chan, W. C., Vose, J. M., Smith, L. M., Armitage, J. O., Mayer, R. A., Pike, B. L., Collins, F. S., et al. (2003) Proc. Natl. Acad. Sci. USA 100, 5372-5377.

Table 4. Unclassified ATM missense changes

*Residue in orthologous mouse ATM gene.

Table 5. Neutral ATM variants detected in MCL

Table 7. Deleterious p53 mutations detected

Table 8. Neutral p53 variants detected in MCL