Monitoring of loss of heterozygosity in serum microsatellite DNA among patients with gastrointestinal stromal tumors indicates tumor recurrence.
BACKGROUND
Patients with gastrointestinal stromal tumors (GIST) harbor increased levels of circulating tumor DNA in their peripheral blood. In the current study, the aim was to investigate whether the frequency of loss of heterozygosity (LOH) on cell-free DNA in blood may reflect tumor stage and recurrent disease of these patients.


METHODS
Serum DNA and follow-up samples of 92 patients suffering from recurrent GIST were analyzed by a PCR-based fluorescence microsatellite analysis using a panel of 12 polymorphic markers. The data were correlated with established risk factors, and patients were followed-up over 4 y.


RESULTS
Microsatellite analysis demonstrated a positive LOH score on cell-free DNA of 30/92 patients. A significant correlation with recurrence in CT imaging showed that a positive LOH score (n ≥ 2) was detected in 58% (11/19) of patients with recurrent disease (P = 0.030, χ(2) test), but only in 25% of patients were clinically free of recurrence. No prognostic significance of a positive LOH score was observed after a median observation time of 48 mo.


CONCLUSIONS
Our findings show that LOH on circulating serum DNA correlates with the tumor status and is a frequent event in GIST patients with recurrent disease.
Rawnaq
Tamina
T
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Schwarzenbach
Heidi
H
Schurr
Paulus G
PG
Freise
Kathrin
K
Brandl
Stephan
S
Izbicki
Jakob R
JR
Kaifi
Jussuf T
JT
D014408:Biomarkers, Tumor / Q000097:blood; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm