The Identification of Chromosomal Translocation, T(4;6)(q22;q15), in Prostate Cancer

Overview

Journal Prostate Cancer Prostatic Dis

Specialties Oncology
Urology

Date 2010 Feb 24

PMID 20177423

Citations 3

Authors

L Shan

L Ambroisine

J Clark

R J Yanez-Munoz

G Fisher

S C Kudahetti

J Yang

S Kia

X Mao

A Fletcher

P Flohr

S Edwards

G Attard

J De-Bono

B D Young

C S Foster

V Reuter

H Moller

T D Oliver

D M Berney

P Scardino

J Cuzick

C S Cooper

Y-J Lu

Affiliations

Soon will be listed here.

Abstract

Our previous work identified a chromosomal translocation t(4;6) in prostate cancer cell lines and primary tumors. Using probes located on 4q22 and 6q15, the breakpoints identified in LNCaP cells, we performed fluorescence in situ hybridization analysis to detect this translocation in a large series of clinical localized prostate cancer samples treated conservatively. We found that t(4;6)(q22;q15) occurred in 78 of 667 cases (11.7%). The t(4;6)(q22;q15) was not independently associated with patient outcome. However, it occurs more frequently in high clinical T stage, high tumor volume specimens and in those with high baseline PSA (P=0.001, 0.001 and 0.01, respectively). The t(4;6)(q22;q15) occurred more frequently in samples with two or more TMPRSS2:ERG fusion genes caused by internal deletion than in samples without these genomic alterations, but this correlation is not statistically significant (P=0.0628). The potential role of this translocation in the development of human prostate cancer is discussed.

Citing Articles

TMPRSS2:ERG fusion gene occurs less frequently in Chinese patients with prostate cancer.

Jiang H, Mao X, Huang X, Zhao J, Wang L, Xu J Tumour Biol. 2016; 37(9):12397-12402.

PMID: 27320318 DOI: 10.1007/s13277-016-5116-9.

The complexity of prostate cancer: genomic alterations and heterogeneity.

Boyd L, Mao X, Lu Y Nat Rev Urol. 2012; 9(11):652-64.

PMID: 23132303 DOI: 10.1038/nrurol.2012.185.

Chromosome rearrangement associated inactivation of tumour suppressor genes in prostate cancer.

Mao X, Boyd L, Yanez-Munoz R, Chaplin T, Xue L, Lin D Am J Cancer Res. 2011; 1(5):604-17.

PMID: 21994901 PMC: 3189822.

References

Panagopoulos I, Strombeck B, Isaksson M, Heldrup J, Olofsson T, Johansson B . Fusion of ETV6 with an intronic sequence of the BAZ2A gene in a paediatric pre-B acute lymphoblastic leukaemia with a cryptic chromosome 12 rearrangement. Br J Haematol. 2006; 133(3):270-5. DOI: 10.1111/j.1365-2141.2006.06020.x. View

Latil A, Chene L, Cochant-Priollet B, Mangin P, Fournier G, Berthon P . Quantification of expression of netrins, slits and their receptors in human prostate tumors. Int J Cancer. 2002; 103(3):306-15. DOI: 10.1002/ijc.10821. View

Cahill D, Kinzler K, Vogelstein B, Lengauer C . Genetic instability and darwinian selection in tumours. Trends Cell Biol. 1999; 9(12):M57-60. View

Mehra R, Tomlins S, Shen R, Nadeem O, Wang L, Wei J . Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol. 2007; 20(5):538-44. DOI: 10.1038/modpathol.3800769. View

Furuta J, Nobeyama Y, Umebayashi Y, Otsuka F, Kikuchi K, Ushijima T . Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas. Cancer Res. 2006; 66(12):6080-6. DOI: 10.1158/0008-5472.CAN-06-0157. View

Tognon C, Knezevich S, Huntsman D, Roskelley C, Melnyk N, Mathers J . Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002; 2(5):367-76. DOI: 10.1016/s1535-6108(02)00180-0. View

Maher C, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X . Transcriptome sequencing to detect gene fusions in cancer. Nature. 2009; 458(7234):97-101. PMC: 2725402. DOI: 10.1038/nature07638. View

Demichelis F, Fall K, Perner S, Andren O, Schmidt F, Setlur S . TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. 2007; 26(31):4596-9. DOI: 10.1038/sj.onc.1210237. View

Karenko L, Hahtola S, Paivinen S, Karhu R, Syrja S, Kahkonen M . Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue. Cancer Res. 2005; 65(18):8101-10. DOI: 10.1158/0008-5472.CAN-04-0366. View

10.

Liu W, Chang B, Cramer S, Koty P, Li T, Sun J . Deletion of a small consensus region at 6q15, including the MAP3K7 gene, is significantly associated with high-grade prostate cancers. Clin Cancer Res. 2007; 13(17):5028-33. DOI: 10.1158/1078-0432.CCR-07-0300. View

11.

Mao X, Young B, Chaplin T, Shipley J, Lu Y . Subtle genomic alterations and genomic instability revealed in diploid cancer cell lines. Cancer Lett. 2008; 267(1):49-54. DOI: 10.1016/j.canlet.2008.03.003. View

12.

Belloni E, Trubia M, Mancini M, Derme V, Nanni M, Lahortiga I . A new complex rearrangement involving the ETV6, LOC115548, and MN1 genes in a case of acute myeloid leukemia. Genes Chromosomes Cancer. 2004; 41(3):272-7. DOI: 10.1002/gcc.20081. View

13.

Mitelman F, Johansson B, Mertens F . The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer. 2007; 7(4):233-45. DOI: 10.1038/nrc2091. View

14.

Watson S, deLeeuw R, Horsman D, Squire J, Lam W . Cytogenetically balanced translocations are associated with focal copy number alterations. Hum Genet. 2006; 120(6):795-805. DOI: 10.1007/s00439-006-0251-9. View

15.

Arakawa H . Netrin-1 and its receptors in tumorigenesis. Nat Rev Cancer. 2004; 4(12):978-87. DOI: 10.1038/nrc1504. View

16.

Perner S, Demichelis F, Beroukhim R, Schmidt F, Mosquera J, Setlur S . TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 2006; 66(17):8337-41. DOI: 10.1158/0008-5472.CAN-06-1482. View

17.

Cuzick J, Fisher G, Kattan M, Berney D, Oliver T, Foster C . Long-term outcome among men with conservatively treated localised prostate cancer. Br J Cancer. 2006; 95(9):1186-94. PMC: 2360576. DOI: 10.1038/sj.bjc.6603411. View

18.

Karan D, Lin M, Johansson S, Batra S . Current status of the molecular genetics of human prostatic adenocarcinomas. Int J Cancer. 2002; 103(3):285-93. DOI: 10.1002/ijc.10813. View

19.

Mehra R, Han B, Tomlins S, Wang L, Menon A, Wasco M . Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res. 2007; 67(17):7991-5. DOI: 10.1158/0008-5472.CAN-07-2043. View

20.

Berger R, Busson M, Baranger L, Helias C, Lessard M, Dastugue N . Loss of the NPM1 gene in myeloid disorders with chromosome 5 rearrangements. Leukemia. 2005; 20(2):319-21. DOI: 10.1038/sj.leu.2404063. View