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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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Histology of coincident prostate cancer foci. Representative H&E stains and illustrations representing the prostate cancer foci that were laser microdissected. Two cancer foci and uninvolved prostate glands were isolated from PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). In addition, a metastatic (Met) focus was isolated from PrCa 18 and PrCa 6. For PrCa 14 (b), the foci were from different levels of the prostate. For the other three specimens the foci were at the same level. Light gray, histologically normal prostate; dark gray, low-grade cancer focus; striped, high-grade cancer focus; checked, metastatic focus from a lymph node removed at the time of prostatectomy.
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fig01: Histology of coincident prostate cancer foci. Representative H&E stains and illustrations representing the prostate cancer foci that were laser microdissected. Two cancer foci and uninvolved prostate glands were isolated from PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). In addition, a metastatic (Met) focus was isolated from PrCa 18 and PrCa 6. For PrCa 14 (b), the foci were from different levels of the prostate. For the other three specimens the foci were at the same level. Light gray, histologically normal prostate; dark gray, low-grade cancer focus; striped, high-grade cancer focus; checked, metastatic focus from a lymph node removed at the time of prostatectomy.

Mentions: Exome sequencing was performed on matched cancer foci and histologically normal prostate glands from four specimens (Fig. 1). To improve the yield of DNA for downstream sequencing, proteinase K digestion was increased to 18 h, 90° incubation was reduced to 30 min and size selection by gel extraction was replaced with size selection with an E-gel or eliminated altogether. On average, 88% of RefSeq coding bases were covered at 10× or greater. A mean of 30.1 somatic coding mutations was identified per cancer focus (Supporting Information Table S1).


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)

Histology of coincident prostate cancer foci. Representative H&E stains and illustrations representing the prostate cancer foci that were laser microdissected. Two cancer foci and uninvolved prostate glands were isolated from PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). In addition, a metastatic (Met) focus was isolated from PrCa 18 and PrCa 6. For PrCa 14 (b), the foci were from different levels of the prostate. For the other three specimens the foci were at the same level. Light gray, histologically normal prostate; dark gray, low-grade cancer focus; striped, high-grade cancer focus; checked, metastatic focus from a lymph node removed at the time of prostatectomy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Histology of coincident prostate cancer foci. Representative H&E stains and illustrations representing the prostate cancer foci that were laser microdissected. Two cancer foci and uninvolved prostate glands were isolated from PrCa 18 (a), PrCa 14 (b), PrCa 6 (c) and PrCa 25 (d). In addition, a metastatic (Met) focus was isolated from PrCa 18 and PrCa 6. For PrCa 14 (b), the foci were from different levels of the prostate. For the other three specimens the foci were at the same level. Light gray, histologically normal prostate; dark gray, low-grade cancer focus; striped, high-grade cancer focus; checked, metastatic focus from a lymph node removed at the time of prostatectomy.
Mentions: Exome sequencing was performed on matched cancer foci and histologically normal prostate glands from four specimens (Fig. 1). To improve the yield of DNA for downstream sequencing, proteinase K digestion was increased to 18 h, 90° incubation was reduced to 30 min and size selection by gel extraction was replaced with size selection with an E-gel or eliminated altogether. On average, 88% of RefSeq coding bases were covered at 10× or greater. A mean of 30.1 somatic coding mutations was identified per cancer focus (Supporting Information Table S1).

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