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Titolo:
Identification of a gene frequently mutated in prostate tumors
Autore:
Reding, DJ; Zhang, KQ; Salzman, SA; Thomalla, JV; Riepe, RE; Suarez, BK; Catalona, WJ; Burmester, JK;
Indirizzi:
Marshfield Clin Fdn Med Res & Educ, Dept Hematol, Marshfield, WI USA Marshfield Clin Fdn Med Res & Educ Marshfield WI USA Marshfield, WI USA
Titolo Testata:
MEDICAL ONCOLOGY
fascicolo: 3, volume: 18, anno: 2001,
pagine: 179 - 187
SICI:
1357-0560(2001)18:3<179:IOAGFM>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CANCER-SUSCEPTIBILITY LOCUS; CHROMOSOME; EPITHELIUM; CELLS;
Keywords:
prostate; tumor suppressor; expressed sequence tag; cell lines; RNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Burmester, JK Marshfield Med Res & Educ Fdn, 1000 N Oak Ave, Marshfield, WI 54449 USA Marshfield Med Res & Educ Fdn 1000 N Oak Ave Marshfield WI USA 54449
Citazione:
D.J. Reding et al., "Identification of a gene frequently mutated in prostate tumors", MED ONCOL, 18(3), 2001, pp. 179-187

Abstract

Although prostate cancer is the second leading cause of cancer death for men in the United States, the genetics of tumor development are poorly understood. Several expressed sequence tagged genes (ESTs) that are expressed predominanlty in the prostate have recently been identified, although their role in the development and maintenance of the prostate is unknown. Here, wedemonstrate that the gene identified as UNIGENE cluster Hs. 104215, which codes for a message found predominanlty in the prostate, may be important in tumor development. We name this gene PCan1 for Prostate Cancer gene 1. Northern blot experiments were performed using RNA isolated from tumor-derived cell lines and human prostate to determine the expression pattern of the gene. DNA sequencing was used to identify mutations that occurred in tumor tissue. By Northern blot analysis, this gene product was not detectable in LNCaP, DU 145, or PC-3 prostate cancer cell lines, although it was readily observed in RNA isolated from total prostate and from dissected central andperipheral regions of prostate. Sequence analysis of genomic DNA from LNCaP, DU 145, or PC-3 cells demonstrated a G/A polymorphism at position 193. Analysis of matched tumor-derived DNA and blood-derived DNA samples from 11 of 13 patients who had undergone a radical prostatectomy and who were homozygous for A in blood-derived DNA demonstrated mutation of position 193 in matched tumor samples resulting in G/A polymorphism. Sixteen additional patient samples were G/A polymorphic in both blood-derived DNA and tumor-derived DNA and two samples were GG in both blood-derived and tumor-derived DNA. Our results suggest that this gene may be a hot spot for mutation in prostate cancer, especially because our radiation hybrid mapping located this gene within a region identified in linkage mapping studies of affected families with prostate cancer. Loss of heterozygosity in prostate tumors has also been reported at the location of PCan1. Further studies to determine the functional role of this candidate tumor suppressor gene are warranted.

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Documento generato il 05/04/20 alle ore 11:26:14