Genetic alterations in bronchial mucosa and plasma DNA from individuals athigh risk of lung cancer

Evidence suggests that the majority of lung cancer patients have tumour-der ived genetic alterations in circulating plasma DNA, and that this may be de veloped as a diagnostic tool. To this end, we have studied 60 individuals a ttending bronchoscopy clinic, with symptoms suspicious of lung cancer, for genetic alterations in bronchial mucosa biopsy (n = 47) and plasma (n = 40) DNA, Thirteen of 47 individuals from whom biopsies were taken displayed al lelic loss of heterozy gosity (LOH) in biopsy DNA for at least 1 of 4 marke rs. All 13 of these individuals had neoplastic tumour cells in their biopsi es and were subsequently diagnosed with cancer. Thirteen of 40 individuals from whom plasma was taken displayed a plasma DNA LOH, and 12 of these 13 i ndividuals were subsequently diagnosed with cancer. LOH in plasma was gener ally representative of LOH in the corresponding biopsy. In terms of sensiti vity, using just 4 markers, biopsy LOH and plasma LOH were found in 13 of 4 4 (30%) and 12 of 29 (41 %), respectively, of those patients subsequently d iagnosed with cancer. Two patients were positive for LOH in plasma samples that pre-dated a diagnosis of cancer by several months. These data suggest that assay of genetic alterations in circulating plasma DNA may be develope d as a useful addition to conventional techniques for the diagnosis of lung cancer. (C) 2001 Wiley-Liss, Inc.