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 c ancer, 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 prospecti ve investigation into the correlation between abnormal plasma DNA and patie nt survival. Patients and methods: Thirty-five patients with SCLC were selected after hi stological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chose n for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for muta tions of the TP53 gene in tumor and plasma DNA. Results: In 25 patients (71%) at least one molecular change precisely match ing that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and pat ients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant diffe rence (P = 0.02) in survival compared with patients bearing only one of the se molecular changes. In 15 cases it was possible to find a correlation eit her between tumor response and disappearance of abnormal plasma DNA, or tum or progression and persistence of plasma DNA alterations. Conclusions: Free plasma DNA with molecular alterations is present to a hig h degree in plasma DNA of SCLC patients and may have a role as a prognostic factor.