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Serrated Adenomas Have a Pattern of Genetic Alterations That Distinguishes Them from Other Colorectal Polyps

¹ Department of Medicine and ² Comprehensive Cancer Center, University of California, La Jolla; ³ Department of Veterans Affairs Research Service, San Diego, California; ⁴ Karolinska Hospital, Stockholm, Sweden; and ⁵ Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan

Requests for reprints: C. Richard Boland, Baylor University Medical Center (H-250), 3500 Gaston Avenue, Dallas, TX 75246. Phone: 214-820-2692; Fax: 214-818-9292. E-mail: Rickbo{at}BaylorHealth.edu

Background: Serrated adenomas are characterized by serrated crypts with dysplasia, and are distinguished from other polyps by their histology, but the genetic basis of serrated adenomas is unknown. We investigated genetic alterations in colorectal polyps to determine if a specific pattern were associated with serrated adenomas.

Methods: Sixty-six small (<10 mm) colorectal polyps were studied, including 11 hyperplastic polyps, 27 serrated adenomas, 9 tubular adenomas, 6 tubulovillous adenomas, and 3 villous adenomas. Allelic imbalance and microsatellite instability were detected by analysis of microsatellites on 5q, 18q, 17p, 2p, and 3p; K-ras mutations were detected by oligonucleotide hybridization.

Results: Each polyp subset had its own characteristic mutational signature. Allelic imbalance of 18q was significantly more common (P < 0.05), whereas allelic imbalance of 5q and K-ras mutations were significantly less common (P < 0.05) in serrated adenomas compared with other polyps. Allelic imbalance of 17p was not found in any polyp.

Conclusions: Serrated adenomas are significantly more likely to have allelic imbalance at 18q than other types of adenomas, and significantly less likely to have allelic imbalance at 5q or K-ras mutations. Serrated adenomas seem to evolve through a different genetic pathway than other types of polyps in the colon.