Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: A prospect for early diagnosis

A major problem in lung cancer is the lack of clinically useful tests for e arly diagnosis and screening of an asymptomatic population by noninvasive d iagnostic procedures. Recent studies have demonstrated the possibility to d etect genetic alterations in plasma or serum DNA from patients with various cancers. However, these data rely on small series of aggressive tumors wit h advanced-stage disease. To determine whether genetic changes in plasma ar e also detectable in patients with limited disease and thereby potentially useful for early detection, we looked for microsatellite instability (allel e shift) and loss of heterozygosity in plasma DNA of 87 stage I-Ill non-sma ll cell lung cancers and 14 controls. Combining two markers with a high rat e of instability (D21S1245) and loss of heterozygosity (FHIT locus), a micr osatellite alteration was observed in 49 of 87 (56%) non-small cell lung ca ncer tumors and in 35 of 87 (40%) plasma samples. Thirty of 49 (61%) of the cases showing tumor alterations also displayed a change in plasma DNA; in addition, 5 patients displayed alterations in plasma samples only. None of the control individuals had genetic changes in plasma. No association was f ound between the frequency of microsatellite alterations in plasma and tumo r stage or histology, Of interest, plasma DNA abnormalities were detectable in 43% of pathological stage I cases and in 45% of tumors up to 2 cm in ma ximum diameter. These findings highlight new prospects for early tumor dete ction by noninvasive screening procedures based on the analysis of genetic changes in plasma.