When good genes go bad and cancer arises, mutation normally gets the blame. But, newer evidence is challenging that one-dimensional view. Epigenetic modifications, such as DNA methylation, can also shut down tumor suppressor genes by causing changes in the chromosomal structure surrounding the gene as noted in this issue's Hot Papers.1,2
John Minna, director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center, Dallas, demonstrated that the gene RASSF1A is lost to methylation, not mutation, in many tumor samples.1 The first clues to this change, which had no apparent relationship to methylation, came from a chromosomal region, known as 3p21.3, that is frequently lost in a variety of tumors, including lung, breast, kidney, head, and neck. The 3p21.3 deletion "was probably the earliest [change] we could detect in preneoplastic tissues, in hyperplasia and dysplasia," says Minna.
Manel Esteller and his group from the ...
