title: Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer.
abstract: Tumorigenesis of colorectal cancer in patients with hereditary non-polyposis colorectal cancer (HNPCC) has been postulated to follow a different pathway from that of sporadic colorectal tumors. A characteristic of HNPCC-associated tumors is the replication error phenotype. We studied tumorigenesis in 8 fresh-frozen and 67 paraffin-embedded colorectal tumors derived from 29 families with HNPCC or a familial aggregation of colorectal cancer. By using intragenic markers, inactivation of the wild-type allele of hMLH1 was shown to occur through loss of heterozygosity and not through a somatic point mutation. Microsatellite instability is very common and occurs early in almost all colorectal tumors from HNPCC patients. Transforming growth factor beta type II receptor (T beta RII) mutations occur in these tumors at a high frequency. Of colorectal cancers from families with HNPCC, 63% have frameshift mutations in T beta RII, compared with 10% of sporadic colorectal cancers. APC and K-RAS mutations appear to be as frequent in the HNPCC tumors as in the sporadic counterpart.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Tannergård
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Weger
authors.forename: M
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: A
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000209:etiology* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D016368:Frameshift Mutation; D011905:Genes, ras; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II