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Left Colon Tumors Differ Genetically from Right

Left Colon Tumors Differ Genetically From Right Colon Tumors

Microarrays suggest that tumors from the left colon differ genetically from tumors from the right colon, according to a presentation on July 13 at the 94th annual meeting of the American Association for Cancer Research (AACR) held in Washington, D.C.

The investigators recommend distinguishing the two sites of origin in clinical trials.

"There are two both genetically and clinically distinct subgroups of colon cancer, tumors in the cecum and in the sigmoid/rectosigmoid," lead investigator Sanne H. Olesen, MSc, a clinical biochemist at Aarhus University Hospital in Denmark, told Medscape.

"The aspect of molecular target treatment opens up [the possibility of] more specifically targeted treatments of the right-sided and the left-sided colon cancers. This might be able to improve the overall survival of patients suffering from colon cancer in the future."

Adenocarcinomas of the right and left side of the large bowel are thought to differ in epidemiology, morphology, and molecular characteristics.

Dr. Oleson's group used Affymetrix GeneChip microarrays to monitor gene expression of about 6,800 known genes in 20 single samples of normal colonic mucosa and in 25 single samples of sporadic Dukes' B and Dukes' C adenocarcinomas from the left colon (sigmoideum and rectosigmoideum) and from the right colon (cecum).

The investigators found differential expression of 58 genes between normal cecum and normal sigmoideum or rectosigmoideum (1.5-fold; P < .01); of 118 genes between normal mucosa and adenocarcinomas of the cecum; of 186 genes between normal mucosa and adenocarcinomas of the sigmoideum or rectosigmoideum (2.8-fold; P < .05); and of 44 unique genes between right- and left-sided adenocarcinomas.

Thirty genes showed parallel expression on both sides from normal mucosa to adenocarcinoma and were therefore considered to be general tumor markers (2.8-fold; P < .05).

Semiquantitative real-time polymerase chain reaction analysis and immunohistochemistry staining of cryo-sections showed excellent reproducibility of the microarray-based findings.

Differences in gene expression between right- and left-sided tumors were not based on microsatellite instability.

"This discovery may explain why some colorectal patients have responded to treatment while others did not," coauthor Torben Orntoft, a professor at Aarhus University, said in a news release. "With new targeted therapies in development, our patients have a better chance of survival."

The authors concluded that right- and left-sided adenocarcinomas should be regarded as separate entities when conducting clinical trials of new serum markers or treatment regimens, especially new treatments directed at specific molecular targets.

The Karen Elise Jensen Foundation, the Danish Research Council, AROS Applied Biotechnology Aps, Aarhus, the John and Birthe Mayer Foundation, the University and County of Aarhus, the Nordic Cancer Union, and the European Union's 5th frameprogram helped support this study.

AROS Applied Biotechnology Aps is owned partly by the County of Aarhus, the University of Aarhus, Dr. Orntoft, and two other scientists.

AACR 94th Annual Meeting: Abstract R1481. Presented July 13, 2003.

Laurie Barclay, MD

Medscape Medical News 2003. © 2003 Medscape

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