Unicryptal loss of heterozygosity in hereditary non-polyposis colorectal cancer

doi:10.1080/00313029400169102

Pathology

Volume 26, Issue 4, 1994, Pages 414-417

https://doi.org/10.1080/00313029400169102 Get rights and content

Summary

DNA mismatch repair genes are responsible for the condition hereditary non-polyposis colorectal cancer (HNPCC). Genomic destabilization caused by failure of DNA mismatch repair leads to the progressive accumulation of somatic mutations and so to accelerated oncogenesis. The aim of this study was to document the rate of background mutational activity in the normal colorectal mucosa of subjects with HNPCC. A naturally occurring model utilizing a genetic polymorphism (O-acetyltransferase) allows the development of unicryptal loss of heterozygosity (LOH) to be detected by means of mild PAS histochemistry and quantified. The rate of unlcrypthl LOH was measured in informative and affected members of 3 HNPCC families and found to be within the expected range. This result is consistent with the finding that normal cells in HNPCC subjects are DNA repair proficient and supports the view that the mutational effects of the HNPCC gene occur selectively within adenomatous epithelium and serve to accelerate the adenoma-carcinoma sequence.

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Unicryptal loss of heterozygosity in hereditary non-polyposis colorectal cancer

Summary

Cell

Cell

Cell

Pathology

Genetic alterations during colorectal-tumor development

N Engl J Med

Mutation and cancer: statistical study of retinoblastoma

Proc Natl Acad Sci USA

Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP)

Oncogene

Clues to the pathogenesis of familial colorectal cancer

Science

Microsatellite instability in cancer of the proximal colon

Science

Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis

Nature

Differences between the O-acetylated sialic acids of the epithelial mucins of human colonic tumours and normal controls:A correlative chemical and histochemical study.

J Histochem Cytochem

Colorectal goblet cell sialomucin heterogeneity: its relation to malignant disease

J Clin Pathol

Gland to gland heterogeneity in histologically normal mucosa of colon cancer patients demonstrated by monoclonal antibodies to tissue-specific antigens

Cancer Res

Monoclonal antibodies to human colorectal epithelium: markers for differentiation and tumour characterization

Int J Cancer

Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry

Nature