Table 3

Probability of observed fixations in a p16 lesion background due to chance

Lesions observed in the same cells with a p16 lesion may either be neutral mutations that are hitchhikers on the selective sweep driven by the p16 lesion, or they may themselves be advantageous and associated with selective sweeps. Because p16 LOH was used as the first putative advantageous lesion to identify the potential hitchhikers, we exclude other 9p loci with LOH as probably occurring as part of the same event that generated the p16 LOH. The background rate of fixations, pb = 0.012, is our best estimate for the probability that a lesion will hitchhike on the selective sweep of a p16 lesion and reach fixation by chance. The exact binomial probability of the observed rate of fixation based on this background binomial probability indicates that some lesions go to fixation more frequently than would be expected by chance. These results suggest that second hits in p16 and lesions in p53 reach fixation more frequently than would be expected if they were simply hitchhikers on the first p16 lesion.

Fixation of lesion coextensive with a p16 lesionBinomial probability that fixations are hitchhikers
p16 methylation<0.01
p16 mutation<0.01
p53 mutation<0.001
17p (p53) LOHa
 TP53, D17S1303, D17S1298<0.001
9q LOH
17q LOH (D17S1294, D17S1293, D17S1290, D17S1301) and TP53Di≥0.05
Aneuploidy and tetraploidy≥0.05
All microsatellite shifts≥0.05
  • a LOH, loss of heterozygosity.