Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients: follow-up study and prognostic significance.
BACKGROUND
Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma DNA and patient survival.


METHODS
Thirty-five patients with SCLC were selected after histological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chosen for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for mutations of the TP53 gene in tumor and plasma DNA.


RESULTS
In 25 patients (71%) at least one molecular change precisely matching that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and patients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant difference (P = 0.02) in survival compared with patients bearing only one of these molecular changes. In 15 cases it was possible to find a correlation either between tumor response and disappearance of abnormal plasma DNA, or tumor progression and persistence of plasma DNA alterations.


CONCLUSIONS
Free plasma DNA with molecular alterations is present to a high degree in plasma DNA of SCLC patients and may have a role as a prognostic factor.
Gonzalez
R
R
Department of Medical Oncology, Clinica Puerta de Hierro, Madrid, Spain.
Silva
J M
JM
Sanchez
A
A
Dominguez
G
G
Garcia
J M
JM
Chen
X Q
XQ
Stroun
M
M
Provencio
M
M
España
P
P
Anker
P
P
Bonilla
F
F
D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000235:genetics* / Q000401:mortality; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000097:blood*; D004276:DNA, Satellite / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D004276:DNA, Satellite