Carolyn E. Cole

A Juvenile Polyposis Tumor Suppressor Locus at 10q22 Is Deleted From Nonepithelial Cells in the Lamina Propria

BACKGROUND & AIMS Juvenile polyps are characterized by an abundant lamina propria that lacks smooth muscle and may contain cystically dilated glands, with epithelium that seems normal and is nondysplastic. Rarely, an autosomal dominant inheritance pattern occurs. The aim of this study was to test the hypothesis that the genetic defect in both sporadic juvenile polyps and hereditary juvenile polyposis involves loss of function for a tumor suppressor gene. METHODS Allelic losses were detected by comparing normal DNA with tumor DNA from a series of 47 juvenile polyps from 16 patients using polymerase chain reaction amplification of microsatellite markers and fluorescent in situ hybridization (FISH). RESULTS Somatic deletions at 10q22 were detected in 39 of 47 juvenile polyps (83%) from 16 unrelated patients with either hereditary or sporadic juvenile polyps, and the minimum overlap localized juvenile polyposis coli to the 3-cM interval D10S219-D10S1696. Fluorescent in situ hybridization shows that the cells affected by deletion mutation reside exclusively in the lamina propria, not in the epithelium. CONCLUSIONS The location of a novel tumor suppressor gene on chromosome 10 that is affected by deletion mutation in the majority of juvenile polyps was mapped. Unlike adenomas and carcinomas of the colonic epithelium, juvenile polyps originate in the lamina propria.

Diffuse nodular lymphoid hyperplasia of the colon: polyposis syndrome or normal variant?

Diffuse nodular lymphoid hyperplasia (DNLH) has long been recognized in the pediatric population and in adults with common variable immunodeficiency (CVID).1 More recently, an association with HIV has been described.2 Little is known about the prevalence, natural history, and clinical significance of DNLH in immunocompetent adults. DNLH is a rare lymphoproliferative disorder of unknown etiology. Typically, numerous polypoid nodules composed of hyperplastic benign lymphoid tissue are present in the small and/or large intestinal mucosa.3 Although often an incidental finding, presentation is variable and depends on the size and extent of the nodules, as well as the presence or absence of underlying immunodeficiency. Treatment is directed at associated conditions because the disorder itself generally requires no intervention. Though considered benign by most investigators, several case reports document an association with malignant intestinal lymphoma.3,4 When DNLH is found predominantly in the colon, it can mimic a variety of polyposis syndromes but does not have the high risk of malignancy of familial adenomatous polyposis (FAP).5 This underscores the importance of obtaining biopsy specimens for histopathologic diagnosis and the need for increased awareness of this poorly understood entity.

Genetic Testing for Colon Cancer

Colorectal cancer remains one of the most common cancers, with more than 130,000 cases diagnosed annually in the United States (1). As a cause of cancer death, it is now second only to lung cancer. Although most colon cancer is sporadic, at least 15% of cases have some inherited component (2). Colon cancer is perhaps the most familial of all cancers. By age 70, the risk of colorectal cancer is only 2% in the low-risk general population, but increases to 8% for a person with one affected first-degree relative, and to 17% when two relatives first-degree relatives are affected (3). The risk increases further to about 60–80% for patients inheriting the genes that cause hereditary nonpolyposis colon cancer (4), and 95–100% for patients with untreated familial adenomatous polyposis (5). Awareness of genetic and other risk factors is important, because there are very effective means now available that could prevent most colon cancer morbidity and mortality.