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Scientists map unstable region of chromosome 11 linked to tumors


Scientists at the University of Pittsburgh in Pennsylvania have mapped a notoriously unstable region of the human genome that may contribute to a number of human cancers. They identified a new gene, called TAOS1, which is overexpressed in malignant cells and may be a factor in how tumors form and progress.

Chromosome rearrangement in an oral cancer cell shown with multi-colored painting probes.

Tumor cells often contain extra copies of a specific region of chromosome 11. Scientists have suspected that this region may be an area of genetic instability that promotes tumor growth and progression.

The region is duplicated in half of all head and neck cancers as well as in breast, bladder and liver cancers. These extra copies are thought to increase the activity of certain genes, leading to the uncontrolled growth of tumor cells.

The new map may help researchers study the link between smoking and cancer. The scientists pinpoint breaks in segments of the genome that promote extra copies of DNA—a process known as 'gene amplification.' These breakpoints may be related to exposure to cigarette smoke, a leading cause of oral cancer.

"We suspect that one of the ways in which smoking-related cancers develop is by chromosome breakage and rearrangement," says Susanne M. Gollin, who led the study at the University of Pittsburgh Graduate School of Public Health.

"Smoking really shatters chromosomes," Gollin adds.

The study reports that over 60 percent of the examined oral cancer cells had extra copies of the region. Researchers studied 30 cell lines from the tumors of oral cancer patients using a new mapping technique called quantitative microsatellite analysis (QuMA).

In one of the tumors, the team found nearly 80 copies of the region compared with the two copies typically found in normal cells. Genes in these copied regions are thought to give cells a "proliferative advantage" that leads to tumor development, the authors report in the study published in Proceedings of the National Academy of Sciences.

The core region of chromosomal band 11q13 contains at least nine different genes. The newly identified TAOS1 gene along with the gene CCND1—which has also been found to be overexpressed in breast cancer—could be "the driving force" in gene amplification, the scientists say.

Gollin plans to further investigate the role of gene amplification in cancer cells. She says the newly discovered gene could become a reliable indicator for diagnosing the progression of tumors and a patient's response to therapy.

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Huang, X. et al. High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci USA 99, 11369-11374 (August 20, 2002).

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