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 -