Molecular nature of chromosome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis

Abstract

Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15-q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.

Identification of a Novel Tumor Suppressor Gene p34 on Human Chromosome 6q25.1

“…For example, human chromosomal region 17q21, which harbors the familial breast cancer susceptibility gene BRCA1, frequently shows LOH in tumors of sporadic and familial breast cancer patients (9,10). Sporadic and familial colon cancer patients also frequently show LOH in chromosomal region 5q21, where the familial adenomatous polyposis susceptibility gene, APC, is located (11).…”

Multiple pigmentierte Basaliome im Capillitium bei Myotonia dystrophia Curschmann-Steinert

“…2). Bisher bekannte Gendefekte wurden beispielsweise für das Gardner-Syndrom, das ebenso wie die Dystrophia myotonica mit multiplen Pilomatrixomen assoziiert sein kann, auf dem langen Arm von Chromosom 5 (q21-q22) gefunden, für das nävoide Basalzellkarzinomsyndrom auf 9q [3,9,10]. Ebenso fanden sich klinisch keine Anhaltspunkte für andere Systemleiden, die mit multiplen Basaliomen und/oder follikulären Hautneoplasmen einhergehen können (nävoides Basalzellkarzinomsyndrom, Gardner-Syndrom).…”

Chromosomal imbalances in small cell carcinomas of the urinary bladder

“…[19][20][21] 5q deletions belong to the most frequent cytogenetic alterations in many tumour types, including carcinomas of the lung, 22 oesophagus, 23 ovary, 24 stomach, 25 and colon. 26 While the adenomatous polyposis coli gene (APC) on 5q21 is affected in a fraction of colonic carcinomas, it is likely that different tumour suppressor genes are relevant in other tumours, since 5q LOH often does not include the APC gene and APC mutations are frequently absent in tumours with LOH including the APC gene. 24,25 Known tumour suppressor genes on 13q include the retinoblastoma gene (rb) and the breast cancer susceptibility gene 2 (BRCA2).…”