Predicting cancer’s spread

July 15, 2011
Bill Schaller

Harvard researchers at Dana-Farber Cancer Institute (DFCI) have found a way that may enable them to predict whether human melanoma tumors are likely to spread.

The scientists report in the July 12 edition of the journal Cancer Cell that they have identified a number of cancer genes that endow the tumor with the ability to metastasize and in testing in melanoma skin cancer, they found six abnormal genes that are both cancer-causing and metastasis-promoting. And one of those genes, ACP5, can be used to predict whether human melanoma tumors are likely to spread.

“Early-stage melanomas are often cured by surgical removal, but in about 10 percent of patients who undergo surgery and are considered cancer-free, the disease recurs in metastatic form and becomes fatal,” says the paper’s senior author, Lynda Chin, a Harvard Medical School professor of dermatology at DFCI and Brigham and Women’s Hospital. “The goal of this study was to see if we could find genetic events within the tumor cells that indicate which patients are at high risk for metastasis.”

The discovery of six genes capable of conferring metastatic ability on melanoma cells “is an important step toward developing prognostic tests for identifying early-stage tumors that are likely to spread and can be treated accordingly,” adds Chin.

To become metastatic and live in foreign regions of the body, tumor cells need to acquire a unique set of survival skills: they must break free of their normal moorings, enter the bloodstream or lymph system, exit through blood or lymphatic vessels, trespass on distant tissue, grow, multiply, and attract a blood supply. Each of these abilities comes courtesy of changes in genes or the system that switches genes on and off.

Traditionally, scientists have thought that cancer cells acquire their malignant potential gradually, as genetic errors accumulate over time: first gaining the ability to divide without cessation, then failing to die on schedule, then becoming able to flake off from their neighbors, etc. This paradigm has been overturned by recent studies led by Chin, which make it clear that some cells gain the genetic elements of metastasis early in their evolution.  Such tumors would, in a sense, be fated to become metastatic. Scientists who knew which genes confer metastatic power could read the tumor’s future at an early stage, enabling doctors to cure the disease by intervening early.

To see if they could identify such genes in melanoma, Chin and her colleagues used two groups of genetically engineered mice — one, whose melanoma tumors never become metastatic, and the other, whose melanomas always do. When they scanned the two sets of melanoma tumors for genetic differences, they found 360 genes whose activity diverged markedly in the metastatic and non-metastatic groups.

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