Calin and Croce, both members of Ohio State's Comprehensive Cancer Center, working with an international team of colleagues, had long suspected that a particular stretch of DNA on chromosome 13 known as a rich source of mutations linked to various malignancies might be the location of other genes important in carcinogenesis. Multiple tests with a portion of that DNA yielded ARLTS1 as a specific new gene.
ARLTS1 belongs to the Ras superfamily of genes that regulates cell growth. Most of the genes in that family are oncogenes, meaning that when activated, they cause cells to grow out of control. ARLTS1, on the other hand, is a tumor suppressor gene a gene that normally helps the body identify and destroy suspicious-looking cells before they undergo malignant transformation and spread. When ARLTS1 is altered, it loses that ability, giving tumors a chance to establish themselves and grow.
To determine the extent to which ARLTS1 appears in various populations, researchers compared tumor tissue or blood samples from 325 patients with different forms of familial or sporadic cases of cancer to the blood of 475 healthy donors or patients with diseases other than cancer. The families, from the United States, France, Italy and Romania, included patients with chronic myeloid leukemia, or thyroid, colorectal, breast, lung or early stage pancreatic cancer.
Through multiple experimental and computational methods, researchers found that mutated ARLTS1 is three times more likely to be present in patients with familial cancers, and two times more likely to be present in random cases of cancer, than it is in the general population.
Calin says normal ARLTS1 activity can be compromised through deletion, mutation or alteration by a chemical change called methylation, adding that defective ARLTS1 also leads to inhibition of apoptosis, or normal cell death.