An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Standard
An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort. / Smith, David Hersi; Christensen, Ib Jarle; Jensen, Niels Frank; Markussen, Bo; Müller, Sven ; Nielsen, Hans Jørgen; Brünner, Nils; Nielsen1,7, Kirsten Vang .
I: BMC Cancer, Bind 13, 13:489, 2013.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort
AU - Smith, David Hersi
AU - Christensen, Ib Jarle
AU - Jensen, Niels Frank
AU - Markussen, Bo
AU - Müller, Sven
AU - Nielsen, Hans Jørgen
AU - Brünner, Nils
AU - Nielsen1,7, Kirsten Vang
N1 - OA
PY - 2013
Y1 - 2013
N2 - Background: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers andfunctions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and havepreviously been implicated in resistance to platinum compounds. The aim of the current investigation is todetermine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations incolorectal cancer (CRC).Methods: Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probeswere constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRCchemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time torecurrence, and local recurrence in rectal cancer) were analyzed by survival statistics.Results: ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patientmaterial, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens,whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain wassignificantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patientswith colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients.Conclusions:ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patientswith colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treatedpatient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC.
AB - Background: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers andfunctions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and havepreviously been implicated in resistance to platinum compounds. The aim of the current investigation is todetermine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations incolorectal cancer (CRC).Methods: Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probeswere constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRCchemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time torecurrence, and local recurrence in rectal cancer) were analyzed by survival statistics.Results: ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patientmaterial, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens,whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain wassignificantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patientswith colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients.Conclusions:ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patientswith colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treatedpatient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC.
U2 - 10.1186/1471-2407-13-489
DO - 10.1186/1471-2407-13-489
M3 - Journal article
C2 - 24144331
VL - 13
JO - B M C Cancer
JF - B M C Cancer
SN - 1471-2407
M1 - 13:489
ER -
ID: 98312899