Allelic loss of Hox11L1 gene locus predicts outcome of gastrointestinal stromal tumors.
Loss of heterozygosity (LOH) in tumors has been described to have prognostic impact. Hox11L1 gene, located on chromosome 2, has a role in proliferation of neuronal myenteric Cajal cells being the progenitor cells of GISTs. The aim was to examine the frequency and prognostic value of allelic loss of Hox11L1 gene locus in GISTs. Tumor and control DNA of 72 GIST patients was extracted after microdissection from tissue sections. Patients underwent surgery between 1992 and 2003 and were histopathologically reclassified. Microsatellite marker D2S286 on chromosomes 2 near Hox11L1 gene locus was used for detection of LOH by PCR and capillary electrophoresis. Survival was calculated by Kaplan-Meier plots. LOH was found in 7 (10%) of 72 GISTs. Fifty-four (75%) cases did not show LOH. Eleven (15%) were homozygous and consequently non-informative. Survival analysis (n=59) revealed a significantly worse tumor-specific and relapse-free survival for GIST patients with LOH in the tumor by univariate analysis (p<0.05 by log-rank test; median follow-up time 37 months). LOH of Hox11L1 gene locus is a useful parameter for prognosis of GIST. The data propose that Hox11L1 has a role in tumorigenesis in GISTs.
Kaifi
Jussuf T
JT
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany. jkaifi@uke.uni-hamburg.de
Wagner
Meike
M
Schurr
Paulus G
PG
Wachowiak
Robin
R
Reichelt
Uta
U
Yekebas
Emre F
EF
Mann
Oliver
O
Vashist
Yogesh
Y
Kleinhans
Helge
H
Link
Bjoern-Christian
BC
Strate
Tim
T
Kalinin
Viacheslav
V
Izbicki
Jakob R
JR
D000483:Alleles; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D018572:Disease-Free Survival; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000628:therapy*; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
D005819:Genetic Markers; D018398:Homeodomain Proteins; C491534:TLX2 protein, human