Fig. 2: Phylogenetic evolutionary analysis to determine the biologically dominant nodule. | Nature Communications

Fig. 2: Phylogenetic evolutionary analysis to determine the biologically dominant nodule.

From: Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis

Fig. 2

Source data are provided as a Source Data file. A. Spatial spread linked to extra-prostatic extension (EPE). Left panel: In patient #1, 5 primary and 2 LN regions encompassing Grade Groups (GG) 2-5 were analyzed. We identified three distinct molecular subtypes. Middle panel: All tumor regions, including the two LN metastases regions, were TMPRSS2:ERG fusion-positive and with heterogeneous prognostic gene signatures. Right panel: TP53 somatic mutation was detected on all tumor regions, except for P5. Key chromosomal alterations, such as 8p loss and 8q gain, were only detected in regions P1, P2, LN1, LN2. Here, the data suggest that primary tumor regions P1, P2 closely resemble LN1, LN2. Additionally, P5 represents a distinct subclone unrelated to other primary regions or LNs. B. Driver alterations in metastasis to LN. Left panel: In patient #33, 8 primary tumor (GG1-5) and 1 LN metastasis region were analyzed. Gray regions (P4,7,8) designate those with low tumor purity that were excluded. We identified three molecular subtypes. Middle panel: All regions were ETS fusion negative except for P1, P8. P4, P7, and P8 regions were excluded due to low tumor content. Right panel: An SPOP mutation was detected only in P1. Driver alterations: FOXA1, ATM frameshift mutations were detected in regions P2, P3, P5, P6, LN1. RB1 loss and MYC gain were seen in P2, P3, P6, and LN1, but not P5. Here, data suggest that primary regions P2, P3, P6, all GG5 regions with cribriform patterns, closely resemble LN1. C. LN metastasis in multiclonal primary disease. Left panel: In patient #41, 4 primary (GG2-5) and 1 LN metastasis region were analyzed. P1, a region of EPE, was taken from the mid prostate and P2-P4 was taken prostate base. We identified three distinct tumor clones. Middle panel: All samples except P3 and P4 were TMPRSS2:ERG fusion-positive. Right panel: P4 had a FOXA1 somatic mutation which was not seen in other regions. Here, data suggest that primary region P1 closely resembles LN1, as both are TMPRSS2:ERG fusion-positive and harbor PTEN loss.

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