Hormone-sensitive prostate cancer: a case of ETS gene fusion heterogeneity.
Fusion of the hormone-regulated gene TMPRSS2 with ERG occurs in 50-70% of prostate cancers; fusions of ETV1 with one of several partners occur in approximately 10% of prostate cancers. These two translocations are mutually exclusive. The presence of subclasses of these chromosomal rearrangements may indicate worse prognosis, with the subclass 2+Edel, which has duplication of TMPRSS2:ERG fusion sequences, indicating particularly poor survival. However as this case shows, significant heterogeneity can exist with ERG and ETV1 rearrangements occurring in both prostate intra-epithelial neoplasia and cancer in the same prostatectomy specimen and with adjacent cancer areas containing a single copy, duplication and even triplication of the rearranged locus. As the majority of ETS gene fusions are hormone regulated, they could explain the pathogenesis underlying exquisitely hormone-sensitive prostate cancer. This is exemplified by the case presented here of a patient diagnosed in 1991 who remains asymptomatic and chemotherapy-naïve after having long-lasting tumour responses to multiple lines of systemic hormonal treatments.
Attard
G
G
The Royal Marsden NHS Foundation Trust, Sutton, UK.
Jameson
C
C
Moreira
J
J
Flohr
P
P
Parker
C
C
Dearnaley
D
D
Cooper
C S
CS
de Bono
J S
JS
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000235:genetics; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; C515553:TMPRSS2-ERG fusion protein, human; D014157:Transcription Factors