Publication

High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers

Castro, E., Jugurnauth-Little, S., Karlsson, Q., Al-Shahrour, F., Pineiro-Yanez, E., Van de Poll, F., Leongamornlert, D., Dadaev, T., Govindasami, K., Guy, M., Eeles, R., Kote-Jarai, Z., UKGPCS Study, EMBRACE Study & IMPACT Study, Nov-2015, In : Annals of Oncology. 26, 11, p. 2293-2300 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Castro, E., Jugurnauth-Little, S., Karlsson, Q., Al-Shahrour, F., Pineiro-Yanez, E., Van de Poll, F., Leongamornlert, D., Dadaev, T., Govindasami, K., Guy, M., Eeles, R., Kote-Jarai, Z., UKGPCS Study, EMBRACE Study, & IMPACT Study (2015). High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. Annals of Oncology, 26(11), 2293-2300. https://doi.org/10.1093/annonc/mdv356

Author

Castro, E. ; Jugurnauth-Little, S. ; Karlsson, Q. ; Al-Shahrour, F. ; Pineiro-Yanez, E. ; Van de Poll, F. ; Leongamornlert, D. ; Dadaev, T. ; Govindasami, K. ; Guy, M. ; Eeles, R. ; Kote-Jarai, Z. ; UKGPCS Study ; EMBRACE Study ; IMPACT Study. / High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. In: Annals of Oncology. 2015 ; Vol. 26, No. 11. pp. 2293-2300.

Harvard

Castro, E, Jugurnauth-Little, S, Karlsson, Q, Al-Shahrour, F, Pineiro-Yanez, E, Van de Poll, F, Leongamornlert, D, Dadaev, T, Govindasami, K, Guy, M, Eeles, R, Kote-Jarai, Z, UKGPCS Study, EMBRACE Study & IMPACT Study 2015, 'High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers', Annals of Oncology, vol. 26, no. 11, pp. 2293-2300. https://doi.org/10.1093/annonc/mdv356

Standard

High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. / Castro, E.; Jugurnauth-Little, S.; Karlsson, Q.; Al-Shahrour, F.; Pineiro-Yanez, E.; Van de Poll, F.; Leongamornlert, D.; Dadaev, T.; Govindasami, K.; Guy, M.; Eeles, R.; Kote-Jarai, Z.; UKGPCS Study; EMBRACE Study; IMPACT Study.

In: Annals of Oncology, Vol. 26, No. 11, 11.2015, p. 2293-2300.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Castro E, Jugurnauth-Little S, Karlsson Q, Al-Shahrour F, Pineiro-Yanez E, Van de Poll F et al. High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. Annals of Oncology. 2015 Nov;26(11):2293-2300. https://doi.org/10.1093/annonc/mdv356


BibTeX

@article{bfd8fdbe82134fdfbfb484a1deaf7117,
title = "High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers",
abstract = "Background: Germline BRCA2 mutations are associated with poorer outcome prostate cancer ( PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations ( CNA) that could aid to the identification of BRCA2- mutated tumours and would assist us to understand their aggressive clinical behaviour. Methods: High- resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non- carriers in combination with unsupervised analysis was used to define copy number features. Results: PCa from BRCA2 germline mutation carriers ( B2T) harbour significantly more CNA than non- carrier tumours ( NCTs) ( P = 14 x 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate ( FDR) and P value <0.01, including CNA in the genomic region containing c- MYC that was present in 89% B2T versus 12.5% NCT ( P = 3 x 10(-4)). Loss of heterozygosity ( LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. Conclusion: The relative high amount of CNAs in morphologically normal prostate tissue of BRCA2 carriers implies a field effect and together with the observed LOH could be used as a marker of PCa risk in these men. Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2- mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.",
keywords = "prostate cancer, germline, BRCA2, CNV, c-MYC, LOH, COMPARATIVE GENOMIC HYBRIDIZATION, EPITHELIAL OVARIAN-CANCER, BRCANESS, RELAPSE, HETEROZYGOSITY, SUSCEPTIBILITY, PROGRESSION, EXPRESSION, SURVIVAL, LOCUS",
author = "E. Castro and S. Jugurnauth-Little and Q. Karlsson and F. Al-Shahrour and E. Pineiro-Yanez and {Van de Poll}, F. and D. Leongamornlert and T. Dadaev and K. Govindasami and M. Guy and R. Eeles and Z. Kote-Jarai and {UKGPCS Study} and {EMBRACE Study} and {IMPACT Study} and Oosterwijk, {J. C.}",
year = "2015",
month = nov,
doi = "10.1093/annonc/mdv356",
language = "English",
volume = "26",
pages = "2293--2300",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers

AU - Castro, E.

AU - Jugurnauth-Little, S.

AU - Karlsson, Q.

AU - Al-Shahrour, F.

AU - Pineiro-Yanez, E.

AU - Van de Poll, F.

AU - Leongamornlert, D.

AU - Dadaev, T.

AU - Govindasami, K.

AU - Guy, M.

AU - Eeles, R.

AU - Kote-Jarai, Z.

AU - UKGPCS Study

AU - EMBRACE Study

AU - IMPACT Study

AU - Oosterwijk, J. C.

PY - 2015/11

Y1 - 2015/11

N2 - Background: Germline BRCA2 mutations are associated with poorer outcome prostate cancer ( PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations ( CNA) that could aid to the identification of BRCA2- mutated tumours and would assist us to understand their aggressive clinical behaviour. Methods: High- resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non- carriers in combination with unsupervised analysis was used to define copy number features. Results: PCa from BRCA2 germline mutation carriers ( B2T) harbour significantly more CNA than non- carrier tumours ( NCTs) ( P = 14 x 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate ( FDR) and P value <0.01, including CNA in the genomic region containing c- MYC that was present in 89% B2T versus 12.5% NCT ( P = 3 x 10(-4)). Loss of heterozygosity ( LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. Conclusion: The relative high amount of CNAs in morphologically normal prostate tissue of BRCA2 carriers implies a field effect and together with the observed LOH could be used as a marker of PCa risk in these men. Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2- mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.

AB - Background: Germline BRCA2 mutations are associated with poorer outcome prostate cancer ( PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations ( CNA) that could aid to the identification of BRCA2- mutated tumours and would assist us to understand their aggressive clinical behaviour. Methods: High- resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non- carriers in combination with unsupervised analysis was used to define copy number features. Results: PCa from BRCA2 germline mutation carriers ( B2T) harbour significantly more CNA than non- carrier tumours ( NCTs) ( P = 14 x 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate ( FDR) and P value <0.01, including CNA in the genomic region containing c- MYC that was present in 89% B2T versus 12.5% NCT ( P = 3 x 10(-4)). Loss of heterozygosity ( LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. Conclusion: The relative high amount of CNAs in morphologically normal prostate tissue of BRCA2 carriers implies a field effect and together with the observed LOH could be used as a marker of PCa risk in these men. Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2- mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.

KW - prostate cancer

KW - germline

KW - BRCA2

KW - CNV

KW - c-MYC

KW - LOH

KW - COMPARATIVE GENOMIC HYBRIDIZATION

KW - EPITHELIAL OVARIAN-CANCER

KW - BRCANESS

KW - RELAPSE

KW - HETEROZYGOSITY

KW - SUSCEPTIBILITY

KW - PROGRESSION

KW - EXPRESSION

KW - SURVIVAL

KW - LOCUS

U2 - 10.1093/annonc/mdv356

DO - 10.1093/annonc/mdv356

M3 - Article

VL - 26

SP - 2293

EP - 2300

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 11

ER -

ID: 34677680