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Distinguishing Right from Left Colon by the Pattern of Gene Expression¹

Genetics Branch [O. K. G., L. M. R., K. N., J. J., J. C., C-J. H., I. R. K.] and Biometric Research Branch [R. S., G. W.], Center for Cancer Research, National Cancer Institute (NCI), and Division of Cancer Prevention [E. H.], NCI, Bethesda, Maryland 20892; Surgery Department, National Naval Medical Center, Bethesda, Maryland 20889 [J. D., P. S.]; Department of Gastrointestinal Oncology, University of Texas-M. D. Anderson Cancer Center, Houston, Texas 77030 [P. L., S. P.]; Department of Preventive Medicine, Creighton University, Omaha, Nebraska [H. L.]; University of Toronto, Toronto, Ontario, M5G 1X5 Canada [S. G.]; Clinical Oncology Research and Development, Pharmacia, Peapack, New Jersey 07977 [A. B.]; and Ovation Pharma, Lincolnshire, Illinois 60015 [G. G.]

Distinct epidemiological and clinicopathological characteristics of colorectal carcinomas (CRCs) based on their anatomical location suggest different risk factors and pathways of transformation associated with proximal and distal colon carcinogenesis. These differences may reflect distinct biological characteristics of proximal and distal colonic mucosa, acquired in embryonic or postnatal development, that determine a differential response to uniformly distributed environmental factors. Alternatively, the differences in the epidemiology of proximal and distal CRCs could result from the presence of different procarcinogenic factors in the ascending versus descending colon, acting on cells with either similar or distinct biological characteristics. We applied cDNA microarray technology to explore the possibility that mucosal epithelium from adult proximal and distal colon can be distinguished by their pattern of gene expression. In addition, gene expression was studied in fetal (17–24 weeks gestation) proximal and distal colon. More than 1000 genes were expressed differentially in adult ascending versus descending colon, with 165 genes showing >2-fold and 49 genes showing >3-fold differences in expression. With almost complete concordance, biopsies of adult colonic epithelium can be correctly classified as proximal or distal by gene expression profile. Only 87 genes were expressed differently in ascending and descending fetal colon, indicating that, although anatomically relevant differences are already established in embryonic colon, additional changes in gene expression occur in postnatal development.

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