Prostate cancer (CaP) is the most commonly diagnosed malignancy and the second leading cause of cancer mortality in males in the United States. The high rate of mortality is associated with widespread metastatic disease.
In 2006, about 234,460 men in the U.S. will be diagnosed with prostate cancer and nearly 27,500 deaths can be attributed to the disease each year.
Classification
prostatic adenocarcinomas
- classical prostatic adenocarcinomas
- prostatic adenoid cystic carcinoma / prostatic basal cell carcinoma
prostate carcinoma with squamous differentiation (15105655)
According to androgen dependance
androgen-dependent prostate cancer
androgen-independent prostate cancer
Abnormal protein expression
aberrant diffuse expression of p63 (18300803)
Molecular biology
DNA microarrays: 12084220
Proteomics: 11721637
Susceptibility
germline MSR1 variants gene coding for macrophage scavenger receptor 1 (12471593)
germline RNASEL (HPC1) gene variants (12145743)
germline BRCA2 mutations (2%)
Locus at 22q12.3 (17047086)
8q24 (Nature Genetics: 38, 652-658, 2006)
LOH
6q15-16.3 (48%) (12967473)
7q31
8p22-p23 LOH (51%-57%) (16470536)
8q
10q23 (PTEN)
11p15
11p12
11q22
11q23-24
12p12-13 (10379873)
13q13-13q14 (41%-86%) (12886522, 11724291)
13q21-22
13q33
16q (31%) (10411092)
18q21
- No 8p22-p23 LOH in high-grade prostatic intraepithelial neoplasia (HGPIN) (16470536)
- The frequency of 8p22 deletion was significantly higher in clinical prostate cancers (CPC) and latent prostate cancers (LPC) than in incidental prostate cancers (IPC) or lesions. (16470536)
- The frequency of LOH at 8p22 and 8p23.1 loci in high-grade tumors was significantly higher than in low-grade tumors in both the LPCs/IPCs and CPCs. (16470536)
- Allelic loss at 8p22 was significantly more frequent in CPC than in IPC and in pT4 CPC than in earlier-stage CPC. (16470536)
- Deletion of 8p is an important event in both the initiation and metastasis of prostate cancer.
- The extremely high frequency of LOH at 8p22-23.1 in high-grade tumors suggests the existence of a novel putative tumor-suppressor gene associated with the progression of prostate cancer.
Somatic mutations
- MAD1L1 at 7p22
Gene copy increase
8q
Aggressiveness
ch. 7
19q
8q gene copy increase
ETSs family gene overexpression
gene fusions of the 5’-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members in prostate cancer (prostatic adenocarcinoma) :
Wnt/beta-catenin pathway deregulation (17691963)
See also
urokinase plasminogen activator (uPA) (PLAU) (MIM.191840)
prostate cancer genomics
References
Prostate cancer genomics: towards a new understanding. Witte JS. Nat Rev Genet. 2009 Feb;10(2):77-82. PMID: 19104501
Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana-Sundaram S, Wei JT, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM. Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 2007 Jan;39(1):41-51. PMID: 17173048
Liu W, Chang B, Sauvageot J, Dimitrov L, Gielzak M, Li T, Yan G, Sun J, Sun J, Adams TS, Turner AR, Kim JW, Meyers DA, Zheng SL, Isaacs WB, Xu J. Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array. Genes Chromosomes Cancer. 2006 Nov;45(11):1018-32. PMID: 16897747
Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, Tchinda J, Tomlins SA, Hofer MD, Pienta KG, Kuefer R, Vessella R, Sun XW, Meyerson M, Lee C, Sellers WR, Chinnaiyan AM, Rubin MA. TMPRSS2:ERG Fusion-Associated Deletions Provide Insight into the Heterogeneity of Prostate Cancer. Cancer Res. 2006 Sep 1;66(17):8337-41. PMID: 16951139
Murillo H, Schmidt LJ, Karter M, Hafner KA, Kondo Y, Ballman KV, Vasmatzis G, Jenkins RB, Tindall DJ. Prostate cancer cells use genetic and epigenetic mechanisms for progression to androgen independence. Genes Chromosomes Cancer. 2006 Jul;45(7):702-16. PMID: 16615098
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005 Oct 28;310(5748):644-8. PMID: 16254181
Reviews
Ellem SJ, Risbridger GP. Treating prostate cancer: a rationale for targeting local oestrogens. Nat Rev Cancer. 2007 Aug;7(8):621-7. PMID: 17611544
Tycko B, Li CM, Buttyan R. The Wnt/beta-catenin pathway in Wilms tumors and prostate cancers. Curr Mol Med. 2007 Aug;7(5):479-89. Review. PMID: 17691963
Hunter DJ, Riboli E, Haiman CA, Albanes D, et al.; National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes. Nat Rev Cancer. 2005 Dec;5(12):977-85. PMID: 16341085
Stecca B, Mas C, Altaba AR. Interference with HH-GLI signaling inhibits prostate cancer. Trends Mol Med. 2005 May;11(5):199-203. PMID: 15882606
Sanchez P, Clement V, i Altaba AR. Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer. Cancer Res. 2005 Apr 15;65(8):2990-2. PMID: 15833820
Schaid DJ. The complex genetic epidemiology of prostate cancer. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21. Epub 2004 Jan 28. PMID: 14749351
Gonzalgo ML, Isaacs WB. Molecular pathways to prostate cancer. J Urol. 2003 Dec;170(6 Pt 1):2444-52. PMID: 14634448
Nelson WG, De Marzo AM, Isaacs WB. N Engl J Med. 2003 Jul 24;349(4):366-81. PMID: 12878745
Nwosu V, Carpten J, Trent JM, Sheridan R. Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum Mol Genet. 2001 Oct 1;10(20):2313-8. PMID: 11673416
Rubin MA. Use of laser capture microdissection, cDNA microarrays, and tissue microarrays in advancing our understanding of prostate cancer. J Pathol. 2001 Sep;195(1):80-6. PMID: 11568894
