Detection of clonal mitochondrial DNA mutation in airway mucosa of follow-up lung cancer patients

A5

Mitochondrial DNA mutations were reported in various cancers but very little is known whether these mutations can be used for diagnostic or prognostic purposes. We examined 30 lesions from 5 follow-up lung cancer patients comprised of tumor, matched airway mucosa, metaplasia and tumor adjacent normal epithelium on high throughput Affymetrix Mitochip 2.0 array platform. The airway mucosal lesions were designated abnormal and suspicious for mild-moderate-severe dysplasia or carcinoma in situ based on Auto-Fluorescence-Bronchoscopy (AFB) and HUGO pathological classification. At least one somatic mutation was detected in each lesion analyzed. A total of 64 mutations were detected with 75% (48/64) from the coding regions and 25% (16/64) from the non-coding regions of the mtDNA. The mutational hot spots were at ND1 (14 mutation) and COI (10 mutations) and 2-4 identical mutations were noted among 4 patients. In 3 out of 5 patients, at least one identical mutation was evident in the tumor and one of the corresponding mucosal lesions. A range of 1-15 tumor matched mutations were detectable in mucosal lesions of the 3 patients. One patient was operated twice for tumor in the right and left lobe respectively within a span of two years and we detected multiple identical mtDNA mutations (20/20) in both the tumors from this patient. Fifteen out of twenty mtDNA mutations detected in the tumors of this patient were also detectable among the 5 corresponding mucosal lesions. Moreover, a significant correlation between smoking and number of mtDNA mutation in these patients were observed (P< 0.02). This is the first study to demonstrate clonal mtDNA mutation in airway mucosa of follow-up lung cancer patients which could be beneficial for disease prognosis and innovative therapeutic interventions. A panel of common mutations among patients may be useful for screening a population at risk and determining the extent of disease in patients with lung cancer.