Loss of 4q21.23-22.1 is a Prognostic Marker for Disease Free and Overall Survival in Non-Small Cell Lung Cancer
Standard
Loss of 4q21.23-22.1 is a Prognostic Marker for Disease Free and Overall Survival in Non-Small Cell Lung Cancer. / Uzunoglu, Faik G; Dethlefsen, Ebba; Hanssen, Annkathrin; Wrage, Michaela; Deutsch, Lena; Harms-Effenberger, Katharina; Vashist, Yogesh K; Reeh, Matthias; Sauter, Guido; Simon, Ronald; Bockhorn, Maximilian; Pantel, Klaus; Izbicki, Jakob R; Wikman-Kocher, Harriet.
In: PLOS ONE, Vol. 9, No. 12, 01.01.2014, p. e113315.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Loss of 4q21.23-22.1 is a Prognostic Marker for Disease Free and Overall Survival in Non-Small Cell Lung Cancer
AU - Uzunoglu, Faik G
AU - Dethlefsen, Ebba
AU - Hanssen, Annkathrin
AU - Wrage, Michaela
AU - Deutsch, Lena
AU - Harms-Effenberger, Katharina
AU - Vashist, Yogesh K
AU - Reeh, Matthias
AU - Sauter, Guido
AU - Simon, Ronald
AU - Bockhorn, Maximilian
AU - Pantel, Klaus
AU - Izbicki, Jakob R
AU - Wikman-Kocher, Harriet
PY - 2014/1/1
Y1 - 2014/1/1
N2 - This study was performed to assess the prognostic relevance of genomic aberrations at chromosome 4q in NSCLC patients. We have previously identified copy number changes at 4q12-q32 to be significantly associated with the early hematogenous dissemination of non-small cell lung cancer (NSCLC), and now aim to narrow down potential hot-spots within this 107 Mb spanning region. Using eight microsatellite markers at position 4q12-35, allelic imbalance (AI) analyses were performed on a preliminary study cohort (n = 86). Positions indicating clinicopathological and prognostic associations in AI analyses were further validated in a larger study cohort using fluorescence in situ hybridization (FISH) in 209 NSCLC patients. Losses at positions 4q21.23 and 4q22.1 were shown to be associated with advanced clinicopathological characteristics as well as with shortened disease free (DFS) and overall survival (OS) (DFS: P = 0.019; OS: P = 0.002). Multivariate analyses identified the losses of 4q21.23-22.1 to be an independent prognostic marker for both DFS and OS in NSCLC (HR 1.64-2.20, all P<0.04), and especially in squamous cell lung cancer (P<0.05). A case report study of a lung cancer patient further revealed a loss of 4q21.23 in disseminated tumor cells (DTCs). Neither gains at the latter positions, nor genomic aberrations at 4q12, 4q31.2 and 4q35.1, indicated a prognostic relevance. In conclusion, our data indicate that loss at 4q21.23-22.1 in NSCLC is of prognostic relevance in NSCLC patients and thus, includes potential new tumor suppressor genes with clinical relevance.
AB - This study was performed to assess the prognostic relevance of genomic aberrations at chromosome 4q in NSCLC patients. We have previously identified copy number changes at 4q12-q32 to be significantly associated with the early hematogenous dissemination of non-small cell lung cancer (NSCLC), and now aim to narrow down potential hot-spots within this 107 Mb spanning region. Using eight microsatellite markers at position 4q12-35, allelic imbalance (AI) analyses were performed on a preliminary study cohort (n = 86). Positions indicating clinicopathological and prognostic associations in AI analyses were further validated in a larger study cohort using fluorescence in situ hybridization (FISH) in 209 NSCLC patients. Losses at positions 4q21.23 and 4q22.1 were shown to be associated with advanced clinicopathological characteristics as well as with shortened disease free (DFS) and overall survival (OS) (DFS: P = 0.019; OS: P = 0.002). Multivariate analyses identified the losses of 4q21.23-22.1 to be an independent prognostic marker for both DFS and OS in NSCLC (HR 1.64-2.20, all P<0.04), and especially in squamous cell lung cancer (P<0.05). A case report study of a lung cancer patient further revealed a loss of 4q21.23 in disseminated tumor cells (DTCs). Neither gains at the latter positions, nor genomic aberrations at 4q12, 4q31.2 and 4q35.1, indicated a prognostic relevance. In conclusion, our data indicate that loss at 4q21.23-22.1 in NSCLC is of prognostic relevance in NSCLC patients and thus, includes potential new tumor suppressor genes with clinical relevance.
U2 - 10.1371/journal.pone.0113315
DO - 10.1371/journal.pone.0113315
M3 - SCORING: Journal article
C2 - 25501003
VL - 9
SP - e113315
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 12
ER -