Hereditary nonpolyposis colorectal cancer (lynch syndromes I and II). II. Biomarker studies

Abstract

Nine families with the cancer family syndrome (CFS), or Lynch syndrome 11, and two with hereditary site-specific colonic cancer (HSSCC), or Lynch syndrome I, were investigated for the following potential biomarkers of genotype status: (1) in ritro tetraploidy of dermal fibroblast monolayer cultures; (2) tritiated thymidine uptake ('HdThd) labeling of colonic mucosa; (3) cytogenetics of peripheral blood mononuclear leukocytes; (4) quantitative serum immunoglobulin determinations; (5) methionine dependence in dermal fibroblasts in tissue culture; (6) segregation analysis; and (7) the study of gene linkage with respect to 25 landmark serum and blood group markers. Positive lod scores of 3.19 for linkage of the J k (Kidd blood group) with CFS were obtained. Both in vitro tetraploidy and 'HdThd uptake in the distal colonic mucosal crypt compartments were positively associated with cancer risk status in CFS and HSSCC kindreds. There was a high incidence of polymorphisms of centromeric heterochromatin, including complete inversion. These findings are of particular clinical and genetic significance because HNPCC lacks premonitory signs of cancer risk. If confirmed, they could conceivably enable definition of genotype as early as birth in members of HNPCC kindreds, thereby epabling psychologic preparation and intensive cancer education for improved compliance in surveillance/management programs. These studies also provide new clues about the chromosome(s) bearing the presumed cancer gene(s). For example, CFS gene(s) may possibly be located on chromosome 2, where J k is located. These biomarkers merit intensive study in additional HNPCC kindreds for a more complete assessment of their sensitivity and specificity. Additionally, essential aspects of previous reports involving biologic samples from these and/or similar subject kindreds are included to permit a comprehensive presentation of the combined findings of this consortium to date.Cuncer 56:939-951, 1985.

Spectral Markers in Preneoplastic Intestinal Mucosa: An Accurate Predictor of Tumor Risk in the MIN Mouse

“…26). Similar findings with proliferation (27) have been observed in he other major autosomal dominant colorectal cancer predisposing syndrome, hereditary nonpolyposis colorectal cancer. Additionally, markers, such as lectin immunohistochemistry, have been noted to be abnormal in the uninvolved mucosa of both FAP and hereditary nonpolyposis colorectal cancer patients (28).…”

DNA mismatch repair: Molecular mechanism, cancer, and ageing

“…Of these, approximately 3-4% occur in familial cancer syndromes of which Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch Syndrome is the most common (Lynch et al, 1985). HNPCC is characterized by an increased risk of colorectal cancer and other cancers.…”

Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications

“…It is also pertinent to note that Lynch et al 54,55 had previously classified families into Lynch syndrome I, which was characterized by families with increased CRC risk but lacking associated extracolonic cancers, and Lynch syndrome II, which contained the associated integral cancers in addition to CRC excess. These studies took place in the 1980s, prior to knowledge about MMR mutations and their causal significance in the Lynch syndrome.…”