How Many Mutations in a Cancer?

Abstract

The role of genomic instability in causing and promoting tumor growth remains controversial. 1,2 Some argue that instability is necessary for tumorigenesis, 3 while others take the view that Darwinian selection is the driving force. 2 It is becoming clear that many cancers harbor multiple mutations, the great majority of which probably have no significant effect on tumor growth. Gross karyotypic abnormalities, 4 widespread microsatellite instability, 5 very frequent allelic loss, 6 and multiple small-scale insertions and deletions 7 have all been found in common types of cancer. Recent estimates have put the total number of mutations in a cancer at more than 10,000. 7 There is, moreover, evidence that some benign 8 or supposedly non-neoplastic 9 lesions harbor many or several mutations, although such findings are by no means universal. The finding of so many mutations has generally been unexpected by most commentators. 10 These data have been taken as evidence to support the central, and perhaps even necessary, role of genomic instability in tumorigenesis. 11