Significant DNA heterogeneity observed
The results showed significant DNA heterogeneity comparing the molecular profiles of primary tumor foci obtained from individual patients. The RNA analyses indicated that low-grade foci tended to cluster together and separately from high-grade foci.
As an example, analyses of samples obtained from one patient who had five primary tumor foci (four high-grade, one low-grade) and two lymph node metastases showed that the primary tumor foci near the positive margin exhibited higher concordance with the lymph node metastases than intraprostatic foci. Comparisons of copy number alterations found in lymph node metastases and primary tumor foci indicated that the biologically dominant nodule that gave rise to metastasis was not necessarily the largest primary lesion or the one with the highest Gleason score.
“Our findings suggest that the expression profile of a low-grade focus cannot predict the presence or lack thereof of a high-grade focus within the same patient,” said Dr. Salami.
“They also indicate that a specific molecular profile might confer metastatic risk more so than lesion grade or size.”
The authors plan to enroll a total of 50 patients in the study and hope data from the larger population might allow them to identify genes that are informative for predicting metastases in individual patients and subsequently the development of a prognostic signature that might be robust to multifocality.
In addition, they are investigating whether magnetic resonance imaging might be helpful for identifying the most biologically significant tumor. Based on the idea that tumor cells found in peripheral blood or urine may reflect the heterogeneity of multiple foci within the prostate, they are conducting studies to see if DNA and RNA sequencing of those fluids, rather than prostate biopsy samples, could provide a better-performing prognostic assay.
Two of Dr. Salami’s co-authors have a financial or other relationship with multiple pharamecutical companies.
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