ROC analysis of the <i>BRCA2</i> signature in the validation set.

<p>Each tumor was given a score that was a weighted sum of the mean centered gene expression levels for each gene in the signature. The validation set contained 19 <i>BRCA2</i> and 12 <i>BRCAX</i> tumors. The AUC was 0.76.</p

GSEA for loss of chromosomal bands.

<p>Footnote. The genes column shows the number of genes used to score the band. The nominal, FDR and FWER p-values were all <0.001. ES, enrichment score; NES normalized enrichment score.</p

<i>BRCA2</i> signature genes.

<p>Footnote. t: moderated t-statistic for 66 genes that best discriminate between <i>BRCA2</i> and <i>BRCAX</i> tumors. p: p-value after Benjamini Hochberg correction (all genes had an unadjusted p-value <0.0001).</p

Contingency table summarizing the FISH data for deletions on chromosomes 13 and 14.

<p>Footnote. “Loss” refers to cases where ≥50% of nuclei had less than the modal ploidy or had ploidy = 1. “Other” refers to cases where the value was <50%. The p value is for a Fisher exact test. The values for “Chr13 and 14” refer to cases where both chromosomes were affected.</p

Characteristics of patients and tumors.

<p>Footnote. Tumor set: Training set, tumors used to create the gene expression signature; Validation set, BRCAX tumors from Bergonie Cancer Institute; Genomic set, tumors only used for CGH and SNP analysis. nd, not determined. There was no statistically significant difference (p>0.05, Fisher test) between the BRCA2 and BRCAX groups for the following comparisons: age at surgery</p

Unsupervised hierarchical clustering of the 66 <i>BRCA2</i> signature genes in the training set.

<p>There are seven <i>BRCA2-</i>mutant tumors and 24 <i>BRCAX</i> tumors (tumors from patients lacking known BRCA1/2 mutations but with a familial history of breast cancer). The upper left quadrant contains many genes on 13q and 14q that show reduced expression in <i>BRCA2</i> tumors.</p

Genomic profiles in the training set.

<p>Upper panels: BAC-CGH profiles of <i>BRCA2</i>-mutant tumors showing gains in red, losses in green and modal copy number in yellow. Lower panels: BAF profiles of <i>BRCA2</i>-mutant tumors on Illumina SNP arrays. The boundaries of the common regions of deletion on chromosomes 13 and 14 are marked by vertical red lines.</p

FISH with probes in the region of common deletion on chromosomes 13 and 14.

<p>Footnote. The table shows the percentage of nuclei with less than the modal ploidy or with ploidy = 1 for both the centromeric and the deletion probes. Tumours A-M were not characterized by CGH.</p

Cumulative rates of gain and loss for tumors analyzed by CGH (red, 4 <i>BRCA2</i>-mutant tumors; black, 24 <i>BRCAX</i> tumors).

<p>A, All chromosomes; B, Chromosome 13; C, Chromosome 14. Each vertical line in B & C corresponds to an individual BAC probe. When the red line reaches −1, all of the tumors showed loss for that probe.</p