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Genetic Changes in Contralateral Bronchioloalveolar Carcinomas of the Lung

Objective: The pattern of metastases and recurrence of bronchioloalveolar carcinoma (BAC) differs from adenocarcinoma of the lung, occurring more frequently within the lung without extrapulmonary involvement. Analyses of genetic differences of contralateral BACs may help to explain these clinical differences. Methods: We compared paired tumors from 5 patients with contralateral metachronous BACs for loss of heterozygosity (LOH) on 6 chromosomal arms (2q, 3p, 5q, 9p, 13q and 17p) and mutational analysis of p53 and K-ras. Results: Two patients, patients 1 and 2, had discordant patterns of LOH on 2 and 3 of the chromosome arms, respectively. In addition, patient 2 had a detectable K-ras mutation in his initial tumor but not in his second. These results suggest that in patients 1 and 2, the contralateral tumors were clonally unrelated. Patient 3 had no mutations in the K-ras or p53 gene and no LOH on any of the 5 informative chromosome arms. Patient 4 had LOH of 9p and mutated K-ras in both the first and the second tumor, with a mutation in the p53 gene in the first but not in the second tumor. Patient 5 had LOH of 17p and the same p53 mutations in both the first and the second tumor, with a mutation of K-ras in the first tumor but not in the second. Conclusions: The preponderance of evidence suggests that in patients 3, 4 and 5, the paired tumors were clonally related. The different patterns of LOH and mutations in clinically similar contralateral metachronous BACs provide evidence of genetic heterogeneity in the tumors of this patient group.