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BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

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BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. / Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G; Bielawski, Krzysztof P; Brandt, Burkhard.

In: CLIN CANCER RES, Vol. 16, No. 13, 13, 2010, p. 3340-3348.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bednarz, N, Eltze, E, Semjonow, A, Rink, M, Andreas, A, Mulder, L, Hannemann, J, Fisch, M, Pantel, K, Weier, H-UG, Bielawski, KP & Brandt, B 2010, 'BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood', CLIN CANCER RES, vol. 16, no. 13, 13, pp. 3340-3348. https://doi.org/10.1158/1078-0432.CCR-10-0150

APA

Bednarz, N., Eltze, E., Semjonow, A., Rink, M., Andreas, A., Mulder, L., Hannemann, J., Fisch, M., Pantel, K., Weier, H-U. G., Bielawski, K. P., & Brandt, B. (2010). BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. CLIN CANCER RES, 16(13), 3340-3348. [13]. https://doi.org/10.1158/1078-0432.CCR-10-0150

Vancouver

Bednarz N, Eltze E, Semjonow A, Rink M, Andreas A, Mulder L et al. BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. CLIN CANCER RES. 2010;16(13):3340-3348. 13. https://doi.org/10.1158/1078-0432.CCR-10-0150

Bibtex

@article{ab9093bbc1ed4c2bb78d651940cc52ed,
title = "BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood",
abstract = "PURPOSE: A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The present analysis was aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in PCa patients.EXPERIMENTAL DESIGN: To map molecular progression in PCa outgrowth, we used fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood.RESULTS: We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (P < 0.05), invasion to pelvic lymph nodes (P < 0.05), as well as biochemical recurrence (P < 0.01). Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites. In four of seven patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs.CONCLUSIONS: Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.",
keywords = "Aged, Chromosomes, Human, Pair 17, Disease Progression, Gene Deletion, Gene Dosage, Humans, Lymphatic Metastasis, Male, Middle Aged, Models, Biological, Neoplasm Metastasis, Prostatic Neoplasms, Translocation, Genetic",
author = "Natalia Bednarz and Elke Eltze and Axel Semjonow and Michael Rink and Antje Andreas and Lennart Mulder and Juliane Hannemann and Margit Fisch and Klaus Pantel and Weier, {Heinz-Ulrich G} and Bielawski, {Krzysztof P} and Burkhard Brandt",
year = "2010",
doi = "10.1158/1078-0432.CCR-10-0150",
language = "English",
volume = "16",
pages = "3340--3348",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "13",

}

RIS

TY - JOUR

T1 - BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

AU - Bednarz, Natalia

AU - Eltze, Elke

AU - Semjonow, Axel

AU - Rink, Michael

AU - Andreas, Antje

AU - Mulder, Lennart

AU - Hannemann, Juliane

AU - Fisch, Margit

AU - Pantel, Klaus

AU - Weier, Heinz-Ulrich G

AU - Bielawski, Krzysztof P

AU - Brandt, Burkhard

PY - 2010

Y1 - 2010

N2 - PURPOSE: A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The present analysis was aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in PCa patients.EXPERIMENTAL DESIGN: To map molecular progression in PCa outgrowth, we used fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood.RESULTS: We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (P < 0.05), invasion to pelvic lymph nodes (P < 0.05), as well as biochemical recurrence (P < 0.01). Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites. In four of seven patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs.CONCLUSIONS: Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.

AB - PURPOSE: A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The present analysis was aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in PCa patients.EXPERIMENTAL DESIGN: To map molecular progression in PCa outgrowth, we used fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood.RESULTS: We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (P < 0.05), invasion to pelvic lymph nodes (P < 0.05), as well as biochemical recurrence (P < 0.01). Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites. In four of seven patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs.CONCLUSIONS: Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.

KW - Aged

KW - Chromosomes, Human, Pair 17

KW - Disease Progression

KW - Gene Deletion

KW - Gene Dosage

KW - Humans

KW - Lymphatic Metastasis

KW - Male

KW - Middle Aged

KW - Models, Biological

KW - Neoplasm Metastasis

KW - Prostatic Neoplasms

KW - Translocation, Genetic

U2 - 10.1158/1078-0432.CCR-10-0150

DO - 10.1158/1078-0432.CCR-10-0150

M3 - SCORING: Journal article

C2 - 20592016

VL - 16

SP - 3340

EP - 3348

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 13

M1 - 13

ER -