Phenotypic Variation in Cancer Cells Often Not Due to Mutations

Jef Akst in The Scientist:

Most models of how tumors evolve have assumed that the process is based predominately on cancer cells’ genetics, and many cancer treatments are specifically targeted to mutations associated with disease. But comparing whole genome sequence data with RNA-seq data from samples of colorectal tumors revealed that the vast majority of gene expression differences among cancer cells cannot be explained by genetics, researchers report in Nature today (October 26).

“So far, a lot of the work that’s been done exploring cancer evolution in cancer development has focused very much on just the genetics,” says Nicholas McGranahan, a computational cancer researcher at the University College London Cancer Institute’s CRUK UCL Centre who was not involved in the research. But according to the new study, “there’s lots of these alterations that they can’t identify a clear [genetic] underpinning for. . . . It’s a nice study because it highlights some of the limitations of what we’ve been doing before.”

Computational biologist Andrea Sottoriva says that it’s those limitations that led him and his colleagues to consider the transcriptome in cancer evolution. “Basically, looking at the genetic evidence was not explaining everything that we were seeing,” says Sottoriva, a group leader at the Institute of Cancer Research, London, and the head of Computational Biology Research Centre at Human Technopole in Milan, Italy. For example, he explains, “if you just look at . . . mutations in genes that are involved in cancer, it’s not very easy to distinguish a benign cancer from a malignant cancer: In a benign cancer, there are as many cancer driver mutations as in a malignant cancer.”

More here.