Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds.

Mutation and selective pressure--cornerstones of Darwin's theory--are the means by which organisms gain an advantageous foothold or pass into oblivion.

In a new study, researchers at ASU's Biodesign Institute led an international team to explore how evolutionary processes guide the pathways of cells.

Their results, which appear in the advanced online edition of Nature Communications, point to influences leading some cells to remain stable over time while driving others to become cancerous and expand without limit.

The new research focuses on a condition known as Barrett's Esophagus (BE).

The disease, which affects over three million Americans, causes cells lining the throat to change shape from their normal form (known as squamous epithelia) to a pathological cell type (known as columnar epithelia).

A small number of BE patients--just .2 percent per year--will go on to develop a highly lethal, treatment-resistant cancer, known as Esophageal Adenocarcinoma (EAC).

Despite advances in therapy, prospects for EAC patients remain bleak--fewer than 15 percent survive beyond 5 years.

"By taking a host of minute samples across the surface of the esophagus, and across many years while these patients were under surveillance to detect cancer, we had an unprecedented view of the dynamics of carcinogenesis," says Carlo Maley, a researcher at the Biodesign Center for Personalized Diagnostics and a senior author of the new study.

Barrett's Esophagus can develop over time when digestive acid backs up from the stomach into the oesophagus, causing damage and growth of precancerous cells.

To accurately assess the evolutionary dynamics involved in progression to cancer, researchers need more fine-grained analyses of BE cells, to tease out details that may not be detectable in whole biopsies containing millions of cells.

Better predictions will rely in part on testing BE samples at multiple points in time, and an examination of cells extracted from different locations in the oesophageal tissue.

One positive consequence of aggressive BE cell surveillance is that it has provided researchers with a rich library of data that can be mined using new methods in order to tease out critical factors governing progression vs non-progression to cancer.

The study addresses five previously unanswered questions concerning BE. 

• BE tissue in most cases arises from a single altered ancestral cell
• expansion of cancerous clones (identical cells of common ancestry) is rare
• cells sampled near the gastro-oesophageal junction accumulate more genomic alterations than those found in other regions of the oesophagus, making them better targets for diagnosis
• there are dramatic changes in mutation rate during progression and these may occur early in the process of cancer progression and
• genetic diversity as measured through biopsy in Barrett's patients is comparable to that observes in individual crypts, indicating that biopsy analysis is adequate for assessing the evolutionary characteristics of BE cells and their likelihood of progression.

Continued work in this area promises to untangle the complex network of evolutionary factors at play when cells are directed away from their normal course and toward the fateful path of cancer.

Source: Arizona State University