PMID- 25501003
OWN - NLM
STAT- MEDLINE
DCOM- 20150928
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 12
DP  - 2014
TI  - Loss of 4q21.23-22.1 is a prognostic marker for disease free and overall survival 
      in non-small cell lung cancer.
PG  - e113315
LID - 10.1371/journal.pone.0113315 [doi]
LID - e113315
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.
FAU - Uzunoglu, Faik G
AU  - Uzunoglu FG
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Dethlefsen, Ebba
AU  - Dethlefsen E
AD  - Institute of Tumour Biology, University Medical Center of Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Hanssen, Annkathrin
AU  - Hanssen A
AD  - Institute of Tumour Biology, University Medical Center of Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Wrage, Michaela
AU  - Wrage M
AD  - Institute of Tumour Biology, University Medical Center of Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Deutsch, Lena
AU  - Deutsch L
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Harms-Effenberger, Katharina
AU  - Harms-Effenberger K
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany; Institute of Tumour Biology, University 
      Medical Center of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Vashist, Yogesh K
AU  - Vashist YK
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Reeh, Matthias
AU  - Reeh M
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Sauter, Guido
AU  - Sauter G
AD  - Department of Pathology, University Medical Center of Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Simon, Ronald
AU  - Simon R
AD  - Department of Pathology, University Medical Center of Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Bockhorn, Maximillian
AU  - Bockhorn M
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Pantel, Klaus
AU  - Pantel K
AD  - Institute of Tumour Biology, University Medical Center of Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Izbicki, Jakob R
AU  - Izbicki JR
AD  - Department of General, Visceral and Thoracic Surgery, University Medical Center 
      of Hamburg-Eppendorf, Hamburg, Germany.
FAU - Wikman, Harriet
AU  - Wikman H
AD  - Institute of Tumour Biology, University Medical Center of Hamburg-Eppendorf, 
      Hamburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141211
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Aged
MH  - Allelic Imbalance
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*diagnosis/*genetics/pathology
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 4/*genetics
MH  - Cohort Studies
MH  - DNA Copy Number Variations
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*diagnosis/*genetics/pathology
MH  - Male
MH  - Microsatellite Repeats/genetics
PMC - PMC4263470
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/12/17 06:00
MHDA- 2015/09/29 06:00
PMCR- 2014/12/11
CRDT- 2014/12/16 06:00
PHST- 2014/03/24 00:00 [received]
PHST- 2014/10/26 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/09/29 06:00 [medline]
PHST- 2014/12/11 00:00 [pmc-release]
AID - PONE-D-14-13025 [pii]
AID - 10.1371/journal.pone.0113315 [doi]
PST - epublish
SO  - PLoS One. 2014 Dec 11;9(12):e113315. doi: 10.1371/journal.pone.0113315. 
      eCollection 2014.