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Low-grade prostate cancer diverges early from high grade and metastatic disease.

VanderWeele DJ, Brown CD, Taxy JB, Gillard M, Hatcher DM, Tom WR, Stadler WM, White KP - Cancer Sci. (2014)

Bottom Line: Notably, mutations in cancer-associated genes and the p53 signaling pathway were found exclusively in high-grade foci and metastases.The pattern of mutations is consistent with early divergence between low- and high-grade foci and late divergence between high-grade foci and metastases.These data provide insights into the development of high-grade and metastatic prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA.

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The molecular relationship of coincident foci. Venn diagrams (left) depicting the pattern of shared and private high-confidence somatic mutations and phylogenetic trees (right) depicting the relationship of coincident foci for PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). The number of high-confidence somatic mutations is labeled within each Venn diagram. In (c), there are no mutations that are shared between the low-grade focus and the metastatic focus and also not shared with the high-grade focus. Within each phylogenetic tree, branch length is proportional to the number of mutations. Gray, uninvolved prostate; blue, low-grade focus; green, high-grade focus; purple, metastatic focus; black, theoretical common progenitor.
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fig03: The molecular relationship of coincident foci. Venn diagrams (left) depicting the pattern of shared and private high-confidence somatic mutations and phylogenetic trees (right) depicting the relationship of coincident foci for PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). The number of high-confidence somatic mutations is labeled within each Venn diagram. In (c), there are no mutations that are shared between the low-grade focus and the metastatic focus and also not shared with the high-grade focus. Within each phylogenetic tree, branch length is proportional to the number of mutations. Gray, uninvolved prostate; blue, low-grade focus; green, high-grade focus; purple, metastatic focus; black, theoretical common progenitor.

Mentions: The vast majority of somatic mutations in low- and high-grade foci were private to the focus in which they were identified. Nine of 79 (11%) high-confidence somatic mutations in the low-grade foci were shared with a high-grade focus, and nine of 139 (7%) high-confidence somatic mutations in the high-grade foci were shared with a low-grade focus (Fig. 3). Capillary sequencing confirmed that these nine shared somatic mutations were not germline variants. In two subjects (14 and 18) all of the mutations were private. In the other two subjects (6 and 25) a small minority of mutations was shared. In contrast to the low-grade foci, 67 of 80 (84%) high-confidence somatic mutations identified in high-grade foci were shared with metastatic disease and metastatic foci had few mutations beyond those identified in high-grade disease (Fig. 3a,c).


Low-grade prostate cancer diverges early from high grade and metastatic disease.

VanderWeele DJ, Brown CD, Taxy JB, Gillard M, Hatcher DM, Tom WR, Stadler WM, White KP - Cancer Sci. (2014)

The molecular relationship of coincident foci. Venn diagrams (left) depicting the pattern of shared and private high-confidence somatic mutations and phylogenetic trees (right) depicting the relationship of coincident foci for PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). The number of high-confidence somatic mutations is labeled within each Venn diagram. In (c), there are no mutations that are shared between the low-grade focus and the metastatic focus and also not shared with the high-grade focus. Within each phylogenetic tree, branch length is proportional to the number of mutations. Gray, uninvolved prostate; blue, low-grade focus; green, high-grade focus; purple, metastatic focus; black, theoretical common progenitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317857&req=5

fig03: The molecular relationship of coincident foci. Venn diagrams (left) depicting the pattern of shared and private high-confidence somatic mutations and phylogenetic trees (right) depicting the relationship of coincident foci for PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). The number of high-confidence somatic mutations is labeled within each Venn diagram. In (c), there are no mutations that are shared between the low-grade focus and the metastatic focus and also not shared with the high-grade focus. Within each phylogenetic tree, branch length is proportional to the number of mutations. Gray, uninvolved prostate; blue, low-grade focus; green, high-grade focus; purple, metastatic focus; black, theoretical common progenitor.
Mentions: The vast majority of somatic mutations in low- and high-grade foci were private to the focus in which they were identified. Nine of 79 (11%) high-confidence somatic mutations in the low-grade foci were shared with a high-grade focus, and nine of 139 (7%) high-confidence somatic mutations in the high-grade foci were shared with a low-grade focus (Fig. 3). Capillary sequencing confirmed that these nine shared somatic mutations were not germline variants. In two subjects (14 and 18) all of the mutations were private. In the other two subjects (6 and 25) a small minority of mutations was shared. In contrast to the low-grade foci, 67 of 80 (84%) high-confidence somatic mutations identified in high-grade foci were shared with metastatic disease and metastatic foci had few mutations beyond those identified in high-grade disease (Fig. 3a,c).

Bottom Line: Notably, mutations in cancer-associated genes and the p53 signaling pathway were found exclusively in high-grade foci and metastases.The pattern of mutations is consistent with early divergence between low- and high-grade foci and late divergence between high-grade foci and metastases.These data provide insights into the development of high-grade and metastatic prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA.

Show MeSH
Related in: MedlinePlus