Genetic translocations and the risk for more aggressive forms of prostate cancer

A research group at Memorial Sloan-Kettering Cancer Center has published data indicating that translocation and/or deletion of the  TMPRSS2-ERG fusion gene  — which occurs in about 50 percent of the cases of clinically localized prostate cancer — is not, in fact, a prognostic indicator of risk for a more aggressive type of disease.

The “New” Prostate Cancer InfoLink regularly cautions readers that an “association” between two clinical facts does not necessarily mean that one is the cause of the other. This research appears to confirm the importance of that caution.

Fine et al. assigned Gleason scores and recorded morphological features for 521 clinically localized prostate cancers sampled in triplicate and arrayed in eight tissue microarray blocks. Fluorescence in situ hybridization (FISH) was then used to delineate TMPRSS2-ERG aberrations.

Their data show that:

  • 217 translocation/deletion cases were detected in the 521 specimens (42 percent) were detected
  • 30 copy number increase-alone cases (5.9 percent) were detected (i.e., 30 patients had ≥ 3 copies of the TMPRSS2-ERG region but no translocation or deletion).
  • of the 217 translocation/deletion cases, 32 had a translocation/deletion and a copy number increase.
  • 237, 200, and 75 cancers had maximum core-specific Gleason scores of 6, 7, and 8-10, respectively.
  • Tumors with a translocation/deletion tended to have lower Gleason scores than those without a translocation/deletion (P = 0.002).
  • Copy number increase cases tended to have higher Gleason scores than those without a copy number increase (P < 0.001).
  • Tumors with a Gleason score of 8-10 were less likely to have a translocation/deletion (odds ratio [OR] = 0.38) and more likely to have a copy number increase alone (OR = 7.33) or  a copy number increase and a translocation/deletion (OR 3.03) compared with tumors with a Gleason score of < 7.

Fine et al. conclude that:

  • TMPRSS2-ERG gene fusion is associated with lower core-specific and overall Gleason scores and not with high-grade morphologies.
  • TMPRSS2-ERG copy number increase, with or without rearrangement, is associated with higher Gleason scores.
  • Translocation/deletion of TMPRSS2-ERG is not associated with histological features of aggressive prostate cancer.

The finding that translocation and/or deletion of the TMPRSSG2-ERG gene fusion alone is not an indicator for aggressive prostate cancer should not be taken to mean that this gene fusion is irrelevant to risk for more aggressive forms of prostate cancer, however. It may be that things are more complicated, and that some other factor, when found in combination with either the increased copy number of the gene fusion or with the translocation and/or deletion of the fused genes, may trigger the risk for more aggressive foms of the disease. It is going to take us a while yet to tease out exactly how specific genetic factors impact risk for aggressive disease.

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