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Allelic Loss of a Common Microsatellite Marker MYCL1

A Useful Prognostic Factor of Poor Outcomes in Colorectal Cancer

¹ Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan; ² Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan; and ³ Department of Pathology, McGill University, Montreal, Quebec, Canada

Purpose: Allelic loss involving chromosome arms 5q, 8p, 17p, and 18q is commonly detected in colorectal cancer (CRC). The short arm of chromosome 1 is also frequently affected in a whole range of cancer types, including CRC. Our aim in the present study was to determine whether allelic losses on 1p were likely to be of much value in predicting the prognosis of CRC cases.

Experimental Design: Genomic DNA was prepared from tumor and corresponding normal tissue specimens from 90 patients who had undergone curative resection for CRC. Loss of heterozygosity (LOH) on chromosome arms 1p, 2p, 5q, 7q, 8p, 17p, 17q, and 18q was examined using 14 microsatellite markers, and possible correlations between LOH and clinicopathological factors (including tumor recurrence and patient survival) were investigated. LOH at the MYCL1 microsatellite marker at 1p34 was detected in 12 of 74 (16.2%) patients who were informative for this marker.

Results: After controlling for tumor stage and gender and excluding findings for patients with remote metastasis, we found that patients who were positive for LOH at MYCL1 were 31 times more likely to experience recurrence than those who were negative for LOH at this locus (95% confidence intervals, 2.27-; P = 0.04). There were indications of a similar tendency for LOH at the 14-3-3--TG microsatellite marker at 1p35, but we could find no evidence of a significant association between LOH at this site and tumor recurrence or patient survival. We were also unable to detect significant association between LOH at the various sites on 2p, 5q, 7q, 8p, 17p, 17q, and 18q and either tumor recurrence or patient survival.

Conclusions: CRC patients whose tumors exhibited LOH at MYCL1 at chromosome 1p34 were likely to have a poor prognosis, suggesting that this marker may have clinical relevance.

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