Mapping of TMPRSS2-ERG fusions in the context of multi-focal prostate cancer.
TMPRSS2-ERG gene fusion leading to the androgenic induction of the ERG proto-oncogene expression is a highly prevalent oncogenic alteration in prostate tumor cells. Prostate cancer is a multi-focal disease, and the origins as well as biological contribution of multiple cancer foci remain unclear with respect to prostate cancer onset or progression. To assess the role of TMPRSS2-ERG alteration in prostate cancer onset and/or progression, we have evaluated the status of fusion transcripts in benign glands, prostatic intraepithelial neoplasia (PIN) and multiple cancer foci of each prostate. Quantitative expression of TMPRSS2-ERG fusion type A and C transcripts was analyzed in benign, tumor and PIN areas, selected from whole-mount radical prostatectomy slides. TMPRSS2-ERG expression was correlated with clinicopathological features. Overall, 30 of 45 (67%) patients exhibited TMPRSS2-ERG fusion transcripts in at least one tumor focus. Of 80 tumor foci analyzed, 39 had TMPRSS2-ERG fusion (type A only: 30, type C only: 2, both types A and C: 7), with predominant detection of the TMPRSS2-ERG fusion type A (27/30, 90%) in the index tumors. Of 14 PIN lesions, 2 were positive for type A fusion. Frequent presence of the TMPRSS2-ERG in index tumors suggests critical roles of ERG alterations in the onset and progression of a large subset of prostate cancer. However, heterogeneity of the TMPRSS2-ERG detection in the context of multiple cancer foci and its frequency in PIN also support the role of other genomic alterations in the origins of prostate cancer.
Furusato
Bungo
B
Department of Surgery, United States Military Cancer Institute, Center for Prostate Disease Research, Uniformed Service University of the Health Science, Bethesda, MD, USA.
Gao
Chun-Ling
CL
Ravindranath
Lakshmi
L
Chen
Yongmei
Y
Cullen
Jennifer
J
McLeod
David G
DG
Dobi
Albert
A
Srivastava
Shiv
S
Petrovics
Gyorgy
G
Sesterhenn
Isabell A
IA
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen