Biomaterial Database

Molecular genetics of hereditary non-polyposis colorectal cancer (HNPCC). 1996

A Cama, and M Genuardi, and G Guanti, and P Radice, and L Varesco

Cattedra di Patologia Generale, Università Gabriele D'Annuzio, Chieti,Italy.

The story of the molecular genetics of HNPCC is one of astonishingly rapid achievements. In just 16 months, from May 1993 to September 1994, four different genes, namely hMSH2, hMLH1, hPMS1 and hPMS2 have been identified and demonstrated to be associated with the disease. Their cloning was facilitated by the finding that tumor cells in HNPCC patients display a hypermutability of DNA short tandem repeats (microsatellite instability). In fact, HNPCC associated genes are the human counterparts of genetic elements known to control the fidelity of DNA replication in lower organisms. So far, more than 50 germline mutations of hMSH2 and hMLH1 genes have been reported in HNPCC kindreds. In addition, somatic mutations have been documented in hereditary as well as sporadic cancers. Unfortunately, the molecular diagnosis of HNPCC is hampered by the lack of mutational "hot spots" and of clearly defined genotype-phenotype correlations and different screening methods are to be employed for the analysis of affected and at-risk individuals.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D003123	Colorectal Neoplasms, Hereditary Nonpolyposis	A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.	Colon Cancer, Familial Nonpolyposis, Type 1,Colorectal Cancer, Hereditary Nonpolyposis, Type 1,Familial Nonpolyposis Colon Cancer Type 1,Hereditary Nonpolyposis Colorectal Cancer,Hereditary Nonpolyposis Colorectal Cancer Type 1,Hereditary Nonpolyposis Colorectal Neoplasms,Lynch Syndrome,Colon Cancer, Familial Nonpolyposis,Colorectal Cancer Hereditary Nonpolyposis,Familial Nonpolyposis Colon Cancer,Hereditary Nonpolyposis Colon Cancer,Lynch Cancer Family Syndrome I,Lynch Syndrome I,Syndrome, Lynch
D004273	DNA, Neoplasm	DNA present in neoplastic tissue.	Neoplasm DNA
D006579	Heterozygote	An individual having different alleles at one or more loci regarding a specific character.	Carriers, Genetic,Genetic Carriers,Carrier, Genetic,Genetic Carrier,Heterozygotes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D018095	Germ-Line Mutation	Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.	Mutation, Germ-Line,Germline Mutation,Germ Line Mutation,Germ-Line Mutations,Germline Mutations,Mutation, Germ Line,Mutation, Germline,Mutations, Germ-Line,Mutations, Germline
D018895	Microsatellite Repeats	A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).	Microsatellite Markers,Pentanucleotide Repeats,Simple Repetitive Sequence,Tetranucleotide Repeats,Microsatellites,Short Tandem Repeats,Simple Sequence Repeats,Marker, Microsatellite,Markers, Microsatellite,Microsatellite,Microsatellite Marker,Microsatellite Repeat,Pentanucleotide Repeat,Repeat, Microsatellite,Repeat, Pentanucleotide,Repeat, Short Tandem,Repeat, Simple Sequence,Repeat, Tetranucleotide,Repeats, Microsatellite,Repeats, Pentanucleotide,Repeats, Short Tandem,Repeats, Simple Sequence,Repeats, Tetranucleotide,Repetitive Sequence, Simple,Repetitive Sequences, Simple,Sequence Repeat, Simple,Sequence Repeats, Simple,Sequence, Simple Repetitive,Sequences, Simple Repetitive,Short Tandem Repeat,Simple Repetitive Sequences,Simple Sequence Repeat,Tandem Repeat, Short,Tandem Repeats, Short,Tetranucleotide Repeat