MARKERS FOR NON-INVASIVE MOLECULAR GENETIC DIAGNOSIS OF ONCOUROLOGICAL DISEASES


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Currently, there is accumulated mass of data on the molecular-genetic disorders in prostate cancer (PCa), bladder cancer (BC) and renal cancer (RC). Tumor cells in these diseases are present in the urine sediment; their number is sufficient for molecular genetic analysis that makes possible the development of noninvasive diagnosis of oncourological diseases. A characteristic feature of PCa includes the overexpression of the PCA3 gene; assay kit Progensa™ to quantify such overexpression has been developed; approximately 50% of tumors express a TMPRSS2-ERG chimeric oncogene. Combined analysis of PCA3 and TMPRSS2-ERG allows to detect PCa with a diagnostic accuracy of 84%, which is significantly higher than that of prostate specific antigen test. As a potential markers of BC, there are somatic mutations in FGFR3, PIK3CA, TERT genes in urine sediment, which are found in this disease with a frequency of about 60, 30 and 50%, respectively. The basis of the test system for DNA diagnosis of BC in urine sediment may include a definition of a combination of mutations in these genes with microsatellite instability. Aberrant methylation of the 5'-regulatory regions of tumor suppressor genes, integrated in the panel, also is considered as a tool in the diagnosis of RC (VHL, RASSF1, RARB2, CDH1), PCa (GSTP1, PTGS2, LGALS3) and BC (RASSF1, APC, SFRP2) after standardization of panels of loci investigated, sample preparation methods, bisulfite conversion, and the design of primers and probes. Thus, a test systems for molecular genetic diagnosis of oncourological diseases in urine sediment are currently available or may be developed in the near future.

Full Text

Restricted Access

About the authors

D. S Mikhaylenko

FSBI «SRI of Urology» of RMPH

PhD in Medical Sciences, Leading Researcher

D. V Perepechin

FSBI «SRI of Urology» of RMPH

O. I Apolikhin

FSBI «SRI of Urology» of RMPH

G. D Efremov

FSBI «SRI of Urology» of RMPH

A. V Sivkov

FSBI «SRI of Urology» of RMPH

References

  1. Злокачественные новообразования в России в 2012 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: ФГБУ «МНИОИ им. П.А. Герцена» Минздрава России. 2014. 250 с.
  2. Mendelsohn J., Howley P.M., Israel M.A. et al. The molecular basis of cancer. 3rd ed. USA (Philadelphia): Elsevier. 2008.
  3. Weinshtein J.N., Akbani R., Broom B.M. et al. Comprehensive molecular characterization of urothelial bladder carcinoma Nature. 2014; 507(7492): 315-322.
  4. Rydzanicz M., Wrzesinski T., Bluyssen H.A., et al. Genomics and epigenomics of clear cell renal cell carcinoma: recent developments and potential applications Cancer Lett. 2013; 341(2): 111-126.
  5. van Tilborg A., Kompier L.C., Lurkin I. et al. Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood PLoS ONE. 2012; 7(8): e43345.
  6. Dimitriadis E., Kalogeropoulos T., Velaeti S. et al. Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer Anticancer Res. 2013; 33(1): 191-197.
  7. Пальцев М.А., Залетаев Д.В. Системы генетических и эпигенетических маркеров в диагностике онкологических заболеваний. М.: Медицина. 2009. С. 153-187.
  8. Fontenete S., Silva J., Teixeira A.L. et al. Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis Int. Braz. J. Urol. 2011; 37(6): 719-726.
  9. Clarke R.A., Zhao Z., Guo A.Y. et al. New genomic structure for prostate cancer specific gene 3 (PCA3) within BMMC1: implication for prostate cancer detection and progression PLoS ONE. 2009; 4(3): e4995.
  10. Killick E., Bancroft E., Kote-Jarai Z., Eeles R. Beyond prostate-specific antigen future biomarkers for the early detection and management of prostate cancer Clin. Oncol. 2012; 24: 545-555.
  11. Ng C.F., Yeung R., Chiu P. et al. The role of urine prostate cancer antigen 3 mRNA levels in the diagnosis of prostate cancer among Hong Kong Chinese patients Hong Kong Med. J. 2012; 18: 459-465.
  12. Tinzl M., Marberger M., Horvath S. et al. DD3PCA3 RNA analysis in urine -a new perspective for detecting prostate cancer Eur. Urol. 2004; 46(2): 185-187.
  13. Durand X., Moutereau S., Xylinas E. et al. Progensa™ PCA3 test for prostate cancer Expert Rev. Mol. Diagn. 2011; 11(2): 137-144.
  14. Capoluongo E., Zambon C.F., Basso D. et al. PCA3 score of 20 could improve prostate cancer detection: results obtained on 734 Italian individuals Clin. Chim. Acta. 2014; 429: 46-50.
  15. Pepe P., Fraggetta F., Galia A. et al. PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35? Int. Braz. J. Urol. 2012; 38(4): 489-495.
  16. Ochiai A., Okihara K., Kamoi K. et al. Clinical utility ofthe prostate cancer gene 3 (PCA3) urine assay in Japanese men undergoing prostate biopsy BJU Int. 2013; 111(6): 928-933.
  17. Bradley L.A., Palomaki G.E., Gutman S. Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer J. Urol. 2013; 190(2): 389-398.
  18. Ramos C.G., Valdevenito R., Vergara I. et al. PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience Urol. Oncol. 2013; 31(8): 1522-1526.
  19. Crawford E.D., Rove K.O., Trabulsi E.J. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases J. Urol. 2012; 188(5): 1726-1731.
  20. Hansen J., Auprich M., Ahyai S.A. Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay Eur. Urol. 2013; 63(2): 201-209.
  21. Tombal B., Andriole G.L., de la Taille A. et al. Clinical judgment versus biomarker prostate cancer gene 3: which is best when determining the need for repeat prostate biopsy? Urology. 2013; 81(5): 998-1004.
  22. De Luca S., Passera R., Milillo A. et al. Histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia do not influence urinary prostate cancer gene 3 score BJU Int. 2012; 110(11 Pt B): E778-E782.
  23. Perdona S., Bruzzese D., Ferro M. et al. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy Prostate. 2013; 73(3): 227-235.
  24. Kirby R., Fitzpatrick J.M. Optimising repeat prostate biopsy decisions and procedures BJU Int. 2012; 109(12): 1750-1754.
  25. Goode R.R., Marshall S.J., Duff M. et al. Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients Prostate. 2013; 73(1): 48-53.
  26. Ferro M., Bruzzese D., Perdona S. et al. Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml PLoS ONE. 2013; 8(7): e67687.
  27. Chevli K.K., Duff M., Walter P. et al. Urinary PCA3 as a Predictor of Prostate Cancer in a Cohort of 3,073 Men Undergoing Initial Prostate Biopsy J. Urol. 2013; doi: 10.1016/j.juro.2013.12.005.
  28. Altintas D.M., Allioli N., Decaussin M. et al. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer PLoS ONE. 2013; 8(6): e66278.
  29. Chan S.W., Nguyen P.N., Violette P. et al. Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers Cancer Med. 2013; 2(1): 63-75.
  30. Young A., Palanisamy N., Siddiqui J. et al. Correlation of urine TMPRSS2:ERG and PCA3 to ERG+ and total prostate cancer burden Am. J. Clin. Pathol. 2012; 138(5): 685-696.
  31. Scheble V.J., Braun M., Beroukhim R. et al. ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor Mod. Pathol. 2010; 23(8): 1061-1067.
  32. Park K., Dalton J.T., Narayanan R. et al. TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia J. Clin. Oncol. 2014; 32(3): 206-211.
  33. Tomlins S.A. Urine PCA3 and TMPRSS2:ERG using cancer-specific markers to detect cancer Eur. Urol. 2014; 65(3): 543-545.
  34. Robert G., Jannink S., Smit F. et al. Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis Prostate. 2013; 73(2): 113-120.
  35. Cornu J.N., Cancel-Tassin G., Egrot C. et al. Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer Prostate. 2013; 73(3): 242-249.
  36. Leyten G.H., Hessels D., Jannink S.A. et al. Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer Eur. Urol. 2014; 65(3): 534-542.
  37. Kompier L.C., Lurkin I., van der Aa M.N. et al. FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy PLoS One. 2010; 5(11): e13821.
  38. van Rhijn B.W., van der Kwast T.H., Liu L. et al. The FGFR3 mutation is related to favorable pT1 bladder cancer J. Urol. 2012; 187(1): 310-314.
  39. van Kessel K.E., Kompier L.C., de Bekker-Grob E.W. et al. FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: a comparison of 3 strategies J. Urol. 2013; 189(5): 1676-1681.
  40. Duenas M., Martinez-Fernandez M., Garcia-Escudero R. et al. PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors Mol. Carcinog. 2013; doi: 10.1002/mc.22125.
  41. Wu S., Huang P., Li C. et al. Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study Eur. Urol. 2014; 65(2): 274-277.
  42. Allory Y., Beukers W., Sagrera A. et al. Telomerase reverse transcriptase promoter mutations in bladder cancer: high frequency across stages, detection in urine, and lack of association with outcome Eur. Urol. 2014; 65(2): 360-366.
  43. Hurst C.D., Platt F.M., Knowles M.A. Comprehensive mutation analysis of the TERT promoter in bladder cancer and detection of mutations in voided urine Eur. Urol. 2014; 65(2): 367-369.
  44. Kinde I., Munari E., Faraj S.F. et al. TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine Cancer Res. 2013; 73(24): 7162-7167.
  45. Guo G., Sun X., Chen C. et al. Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation Nat. Genet. 2013; 45(12): 1459-1463.
  46. Volanis D., Papadopoulos G., Doumas K. et al. Molecular mechanisms in urinary bladder carcinogenesis J. BUON. 2011; 16(4): 589-601.
  47. Liang J.F., Zheng H.X., Li N. et al. Fluorescent microsatellite analysis of urine sediment in patients with urothelial carcinoma Urol. Int. 2010; 85(3): 296-303.
  48. van Tilborg A.A., Kompier L.C., Lurkin I. et al. Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood PLoS One. 2012; 7(8): e43345.
  49. Costa V.L., Henrique R., Ribeiro F.R. et al. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors. BMC Cancer. 2007; 7: 133.
  50. Banks R.E., Tirukonda P., Taylor C. et al. Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer Cancer Res. 2006; 66(4): 2000-2011.
  51. Chao C., Chi M., Preciado M. et al. Methylation markers for prostate cancer prognosis: a systematic review Cancer Causes Control. 2013; 24(9): 1615-1641.
  52. Gao T., He B., Pan Y. et al. The association of retinoic acid receptor beta2(RARß2) methylation status and prostate cancer risk: a systematic review and meta-analysis PLoS One. 2013; 8(5): e62950.
  53. Dimitriadis E., Kalogeropoulos T., Velaeti S. et al. Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer Anticancer Res. 2013; 33(1): 191-197.
  54. Phe V., Cussenot O., Roupret M. Methylated genes as potential biomarkers in prostate cancer BJU Int. 2010; 105(10): 1364-1370.
  55. Hill M., Mazal D., Biron V.A. et al. Promoter methylation in prostate cancer and its application for the early detection of prostate cancer using serum and urine samples Biomark. Cancer. 2010; 2010(2): 17-33.
  56. Wu T., Giovannucci E., Welge J. et al. Measurement of GSTP1 promoter methylation in body fluids may complement PSA screening: a metaanalysis Br. J. Cancer. 2011; 105(1): 65-73.
  57. Besaratinia A., Cockburn M., Tommasi S. Alterations of DNA methylome in human bladder cancer Epigenetics. 2013; 8(10): 1013-1022.
  58. Scher M.B., Elbaum M.B., Mogilevkin Y. et al. Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer J. Urol. 2012; 188(6): 2101-2107.
  59. Serizawa R.R., Rafkiaer U., Steven K. et al. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events Int. J. Cancer. 2011; 129(1): 78-87.
  60. Kandimalla R., Masius R., Beukers W. et al. A 3-plex methylation assay combined with the FGFR3 mutation assay sensitively detects recurrent bladder cancer in voided urine Clin. Cancer Res. 2013; 19(17): 4760-4769.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2014 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies