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Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP

Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP
Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP
Although chromosome translocations are well-documented recurrent events in hematological malignancies and soft tissue sarcomas, their significance in carcinomas is less clear. We report here the molecular characterization of the reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line, LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11-290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1 map. This was further refined to a 580-bp region by Southern blot analysis. A 2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61 and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of the der(15) showed loss of chromosome material proximal to the breakpoint on chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence we conclude that this translocation does not result in an in-frame gene fusion. Comparative expressed sequence hybridization (CESH) and comparative genomic hybridization (CGH) analysis, showed relative down-regulation of gene expression surrounding the breakpoint, but no gross change in genomic copy number. Real-time quantitative RT-PCR for genes around the breakpoint supported the CESH data. Therefore, here we may have revealed a gene down-regulation mechanism associated with a chromosome translocation, either through small deletion at the breakpoint or through another means of chromosome domain related gene regulation.
1424-8581
45-52
Strefford, J.C.
3782b392-f080-42bf-bdca-8aa5d6ca532f
Lane, T.M.
157e1613-5105-4022-a457-56585534ebc0
Hill, A.
4b370ab2-fca3-49d8-a798-4b6f4c0e69c6
LeRoux, L.
c2a2efbd-9cc3-4613-8152-10dfc122a802
Foot, N.J.
e1050e82-3bbc-44b3-9521-e625ec1e73e2
Shipley, J.
2c53e7f0-8721-4460-8168-4fde68fe85d1
Oliver, R.T.
c94e70d8-3276-4ccb-964f-4b06cda706f2
Lu, Y.J.
25cfc4dc-ff88-496d-b21a-f8b2c83e1dcf
Young, B.D.
d1da70f6-c6c3-4155-9bd8-54b73732cb01
Strefford, J.C.
3782b392-f080-42bf-bdca-8aa5d6ca532f
Lane, T.M.
157e1613-5105-4022-a457-56585534ebc0
Hill, A.
4b370ab2-fca3-49d8-a798-4b6f4c0e69c6
LeRoux, L.
c2a2efbd-9cc3-4613-8152-10dfc122a802
Foot, N.J.
e1050e82-3bbc-44b3-9521-e625ec1e73e2
Shipley, J.
2c53e7f0-8721-4460-8168-4fde68fe85d1
Oliver, R.T.
c94e70d8-3276-4ccb-964f-4b06cda706f2
Lu, Y.J.
25cfc4dc-ff88-496d-b21a-f8b2c83e1dcf
Young, B.D.
d1da70f6-c6c3-4155-9bd8-54b73732cb01

Strefford, J.C., Lane, T.M., Hill, A., LeRoux, L., Foot, N.J., Shipley, J., Oliver, R.T., Lu, Y.J. and Young, B.D. (2006) Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP. Cytogenetic and Genome Research, 112 (1-2), 45-52. (doi:10.1159/000087512).

Record type: Article

Abstract

Although chromosome translocations are well-documented recurrent events in hematological malignancies and soft tissue sarcomas, their significance in carcinomas is less clear. We report here the molecular characterization of the reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line, LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11-290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1 map. This was further refined to a 580-bp region by Southern blot analysis. A 2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61 and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of the der(15) showed loss of chromosome material proximal to the breakpoint on chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence we conclude that this translocation does not result in an in-frame gene fusion. Comparative expressed sequence hybridization (CESH) and comparative genomic hybridization (CGH) analysis, showed relative down-regulation of gene expression surrounding the breakpoint, but no gross change in genomic copy number. Real-time quantitative RT-PCR for genes around the breakpoint supported the CESH data. Therefore, here we may have revealed a gene down-regulation mechanism associated with a chromosome translocation, either through small deletion at the breakpoint or through another means of chromosome domain related gene regulation.

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Published date: 2006

Identifiers

Local EPrints ID: 26629
URI: http://eprints.soton.ac.uk/id/eprint/26629
ISSN: 1424-8581
PURE UUID: d64e65bb-db4e-485d-b16f-077c68350d68
ORCID for J.C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 10 Apr 2006
Last modified: 19 Nov 2019 01:47

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