High-resolution analysis of DNA copy number alterations in rectal cancer: correlation with metastasis, survival, and mRNA expression.
OBJECTIVE
This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer.


METHODS
Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina single-nucleotide polymorphism (SNP) arrays. Endpoints of the study were metastasis-free survival (MFS) and cancer-specific survival (CSS).


RESULTS
The median follow-up was 102 months (1-146). Deletions of 8p and 1p36-35 correlated with worse MFS (p = 0.005 and p = 0.01, respectively) and CSS (p = 0.001 and p = 0.01, respectively). Multivariate analysis identified 8p deletion as an independent prognostic factor for MFS (p = 0.04) and CSS (p = 0.003); 97 genes located on the 8p chromosome were significantly underexpressed in tumors with 8p deletion.


CONCLUSIONS
This study shows for the first time in rectal cancer an independent correlation of 8p deletion with MFS and CSS and highlights potential new tumor suppressor genes.
Department of Radiation Oncology, Centre Antoine-Lacassagne, 33 avenue de Valombrose, 06189, Nice, France, doyen@unice.fr.
Jérôme
J
Doyen
Eric
E
Letouzé
Laetitia
L
Marisa
Aurélien
A
de Reyniès
Gérard
G
Milano
Marie-Christine
MC
Etienne-Grimaldi
Sylviane
S
Olschwang
Jochen
J
Gaedcke
Michael
M
Ghadimi
Jean-Pierre
JP
Gérard
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015995:Prevalence; D012333:RNA, Messenger / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000532:radiotherapy; D012307:Risk Factors; D013223:Statistics as Topic; D015996:Survival Rate; D016896:Treatment Outcome
D005819:Genetic Markers; D012333:RNA, Messenger