Histogram of the distribution of methylome-similarity score (MS) between unrelated PT/LR pairs.

<p>MS score for matched pairs is represented by circles. The vertical dashed line corresponds to the 95% quantile of the distribution of the MS scores for the unrelated pairs, used as a threshold to define clonal pairs ().</p

Comparison of classification methods for clonality between pairs in the PT/LR cohort.

<p><b>Cor</b> (Correspondence): correspondence number with the Bollet/Servant cohort. <b>scores</b>: scores obtained with partial identity (PIS) or methylation (MS). <b>Time</b>: time elapsed between diagnosis of the PT and diagnosis of the recurrence. <b>Classification</b>: classification of the recurrence based on copy number (PIS), methylation (MS) or clinical features (clinical). <b>Divergence</b>: which method deviated from the others.</p

Correlation between methylation and copy-number scores.

<p>The horizontal red line (resp. vertical dashed blue line) corresponds to the 95% quantile of the distribution of the methylation-scores (resp. partial identity scores) for the unrelated pairs: (resp. ). PT/AM (resp. PT/LR, resp. PT/CL) pairs are colored in yellow (resp. blue, resp. pink). The black line corresponds to the linear regression between methylation and copy-number scores for all the datasets.</p

Summarized PT/LR Clinical and histological features.

<p><b>Cor</b> (Correspondence): correspondence number with the Bollet/Servant cohort from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103986#pone.0103986-Bollet1" target="_blank">[16]</a>, <b>Type</b>: histological type of the tumor (D =  ductal, L =  lobular), <b>Grade</b>: Aggressiveness of the tumor (1 to 3), <b>ER</b>: presence of estrogen receptors, <b>PR</b>: presence of progesterone receptors, <b>HER2</b>: presence of HER2 receptors, <b>Loc</b> (Location): 1 if the recurrence was located less than 4cm from the PT.</p

Significantly differentially methylated genes between PT and AM samples.

<p><b>CpG</b>: CpG probe name. <b>Gene</b>: Associated gene. <b>Pvalue</b>: FDR corrected p-value. <b>Methylation Variation</b>: Mean variation of methylation from the primary tumor to the axillary metastasis.</p

Kaplan-Meier estimates of the metastasis-free survival between TR and NP for the different classification methods.

<p>The full black (resp. green) line corresponds to the survival for samples classified as TR (resp. NP) and the corresponding dashed lines correspond to upper and lower 95 CI. The red crosses represent censored data. Panel A (resp. B, resp. C) represent the methylation-based (resp. copy-number based, resp. clinical based) classification.</p

Summarized PT/AM Clinical and histological features.

<p><b>Age</b>: Age of the patient at diagnosis of the primary tumor in years, <b>Type</b>: histological type of the tumor (D =  ductal, L =  lobular, Meta = Metaplasia), <b>Grade</b>: Aggressiveness of the tumor (1 to 3), <b>ER</b>: presence of estrogen receptors, <b>PR</b>: presence of progesterone receptors, <b>HER2</b>: presence of HER2 receptors.</p

Study of similarity between matched primary tumors and recurrences by hierarchical clustering.

<p>Hierarchical clustering based on the manhattan distance between methylome profiles with complete linkage was performed. Real pairs that are closer to each other than to any other samples are underlined. Panel A (resp. B, resp. C) represents the PT/AM (resp. PT/LR, resp. PT/CL) set.</p

Pairwise methylome distance for each samples.

<p>Each boxplot represents the Manhattan distance between primary tumor and an unrelated locoregional evolution, or the Manhattan distance between locoregional evolution i and an unrelated primary tumor. The black square represent the Manhattan distance between the matched primary tumor and locoregional evolution from sample . The yellow (resp. blue, resp. pink) panel represents the PT/AM (resp. PT/LR, resp. PT/CL) set. The last panel represents the distribution of distances between the healthy breast tissue and all the other healthy breast tissues from the cohort.</p

Summarized PT/CL Clinical and histological features.

<p><b>Type</b>: histological type of the tumor (D =  ductal, L =  lobular, Med = Medullary, Meta = Metaplasic), <b>Grade</b>: Aggressiveness of the tumor (1 to 3), <b>ER</b>: presence of estrogen receptors, <b>PR</b>: presence of progesterone receptors, <b>HER2</b>: presence of HER2 receptors.</p