Datasets:

Brizape

/

Variome_split_0404_dev

like 0

[ "Aim" ]

[ 0 ]

[ "(A)", "Representative", "F-SSCP", "gel", "used", "to", "detect", "BRAF", "mutationsin", "colorectal", "cancer.", "WT,", "wild-type;", "M,", "mutation.", "(B)", "DNA", "sequencing", "gel", "resultconfirms", "the", "presence", "of", "a", "1799T", "to", "A", "mutation", "giving", "rise", "to", "the", "V600E", "mutation." ]

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[ "Note:", "no", "result", "for", "KRAS", "in", "one", "sessile", "serrated", "adenoma", "(SSA)", "and", "one", "tubular", "adenoma", "(TA)", "or", "for", "BRAF", "in", "one", "mutation", "serrated", " ", "adenoma", "had", "two", "KRAS", "mutations", "in", "codon", "12", "(G→T", "at", "position", "35", "and", "T→G", "at", "position", "36).", "BRAF", "mutation", "at", "V600E", "could", "be", "assessed", "in", "all", "polyps", "except", "for", "a", "single", "TA", "<", " ", "10", "mm.", "BRAF", "mutation", "was", "found", "in", "82", "of", "189", "polyps", "(43%).", "BRAF", "and", "KRAS", "mutations", "were", "negatively", "correlated,", "with", "only", "four", "polyps", "having", "both", "mutations", "(two", "TAs,", "one", "TVA", "and", "one", "SSA).", "The", "three", "conventional", "adenomas", "with", "mutations", "of", "both", "BRAF", "and", "KRAS", "were", "among", "only", "four", "adenomas", "that", "had", "any", "BRAF", "mutations", "at", "all.", "Mutation", "frequencies", "for", "both", "KRAS", "and", "BRAF", "were", "distributed", "differently", "across", "the", "seven", "polyp", "groups", "(Table", "1)." ]

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[ "The", "study", "design", "was", "approved", "by", "the", "medical", "ethical", "committee", "of", "the", "Erasmus", "MC", "Rotterdam,", "the", "Netherlands", "(MEC", "02.949).", "Tissue", "of", "75", "ovarian", "cancer", "patients", "and", "four", "normal", "stromal", "ovarian", "tissues", "collected", "at", "the", "Erasmus", "MC", "in", "Rotterdam", "were", "included", "in", "this", "study.", "The", "patient", "and", "tumor", "characteristics", "are", "listed", "in", "Table", "1.", "Forty-six", "patients", "received", "platinum-based", "chemotherapy", "of", "whom", "34", "responded", "to", "treatment", "defined", "as", "complete", "response,", "partial", "response,", "stable", "disease", "ovarian", " ", "cancer", "cell", "line", "A2780", "has", "been", "cultured", "separately", "in", "two", "different", "research", "laboratories", "at", "our", "department.", "The", "isolated", "DNA", "and", "RNA", "from", "each", "culture", "were", "used", "for", "further", "analysis." ]

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[ "Jass", "J", "R,", "Baker", "K,", "Zlobec", "I,", "Higuchi", "T,", "Barker", "M,", "Buchanan", "D", "&", "Young", "J", "(2006)", "Histopathology", "49,", "121–131" ]

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[ "Of", "the", "17", "CRC", "patients", "with", "the", "Lys618Ala", "variant,", "two", "had", "MSI", "(11.8%),", "one", "in", "the", "familial", "CRC", "group", "(1/8)", "and", "one", "in", "the", "sporadic", "CRC", "group", "(1/9)." ]

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[ "The", "selection", "of", "patients", "included", "in", "this", "study", "was", "based", "on", "the", "completeness", "of", "analyses", "of", "both", "APC", "and", "K-ras", "genes", "as", "well", "as", "hMLH1", "expression", "and", "this", "led", "to", "a", "considerable", "reduction", "in", "the", "number", "of", "cases", " ", "that", "could", "be", "included", "in", "the", "analyses", "presented", "in", "this", "study.", "The", "largest", "reduction", "(72", "cases)", "was", "due", "to", "incompleteness", "of", "the", "analysis", "of", "all", "fragments", "comprising", "the", "APC", "mutation", "cluster", "region.", "Tumour", "DNA", "was", "derived", "from", "formalin-fixed,", "paraffin-embedded", "tumour", "tissue", "blocks.", "Depending", "on", "the", "conditions", "of", "fixation", "and", "storage,", "the", "extracted", "DNA", "is", "more", "or", "less", "fragmented,", "which", "may", "have", "impaired", "the", "analysis", "of", "mutations", "in", "the", "APC", "gene", "more", "than", "in", "the", "K-ras", "gene,", "since", "the", "analysis", "of", "the", "latter", "is", "based", "on", "the", "amplification", "of", "a", "smaller", "gene", "fragment.", "It", "should", "be", "emphasized", "that", "characteristics", "of", "patients", "(age,", "sex,", "family", "history", "of", "colorectal", "cancer)", "and", "tumours", "(sub-localisation,", "Dukes'", "stage", "and", "differentiation)", "of", "the", "group", "under", "study", "are", "similar", "to", "the", "737", "patients", "for", "whom", "tumour", "material", "was", "available", "and", "to", "all", "819", "patients", "initially", "recognized", "within", "the", "cohort", "(data", "not", "shown).", "Moreover,", "the", "K-ras", "and", "hMLH1data", "presented", "here", "are", "similar", "to", "the", "data", "for", "K-ras", "and", "hMLH1", "based", "on", "the", "complete", "groups", "(737", "and", "724", "cases,", "respectively)", "(data", "not", "shown)." ]

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[ "We", "observed", "increased", "expression", "of", "genes", "in", "chromosomal", "region", "12q14.2-12q22", "(see", "Figures", "15,", "16,", "17).", "The", "MDM2", "gene", "at", "12q15", "is", "a", "possible", "target", "of", "this", "misregulation.", "However,", "within", "this", "large", "region", "there", "is", "a", "smaller", "region", "at", "12q21.1-q21.2", "spanning", "eight", "genes", "that", "exhibit", "exceptionally", "high", "expression", "in", "our", "tumor", "samples.", "Among", "these", "is", "LGR5", "Patient", " ", "codes", "are", "given", "on", "the", "vertical", "axis.", "The", "legend", "depicts", "which", "colors", "code", "for", "which", "expression", "changes", "on", "a", "loge", "scale", "(green:", "down", "in", "tumor;", "red:", "up", "in", "tumor).", "View", "in", "conjunction", "with", "Figures", "13", "and", "14." ]

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[ "DNA", "mismatch", "repair", "(MMR)", "is", "divided", "into", "three", "steps:", "initiation,", "excision", "and", "resynthesis", "(Figure", "1).", "Several", "proteins", "are", "involved", "in", "the", "initiation", "of", "MMR", "including", "the", "three", "MutS-homologs,", "MSH2,", "MSH3", "and", "MSH6.", "The", "MutS", "homologs", "form", "a", "heterodimer", "that", "recognizes", "DNA", "damage;", "the", "MSH2", "and", "MSH6", "dimer", "(the", "hMutSα", "complex)", "recognizes", "base-base", "mismatches", "and", "single", "base", "loops", "whereas", "the", "MSH2", "and", "MSH3", "dimer", "(hMutSβ", "complex)", "recognizes", "insertion/deletion", "loops", "of", "more", "then", "one", "base.", "After", "the", "recognition", "of", "the", "DNA", "damage", "the", "binding", "of", "a", "heterodimer", "of", "the", "MutS-homologs", "MLH1", "and", "PMS2", "(the", "hMutLα", "complex)", "leads", "to", "the", "further", "initiation", "of", "MMR.", "Other", "known", "and", "still", "unknown", "proteins", "involved", "in", "the", "last", "two", "steps", "of", "MMR,", "the", "excision", "of", "the", "damaged", "strand", "and", "the", "resynthesis,", "are", "recruited", "subsequently.", "Proteins", "known", "to", "be", "involved", "are", "exonuclease", "ExoI,", "proliferating", "cell", "nuclear", "antigen", "(PCNA),", "DNA", "polymerase", "δ", "and", "perhaps", "ε", "and", "in", "addition", "based", "on", "its", "association", "with", "DNA", "polymerase", "δ", "and", "PCNA,", "DNA", "ligase", "I", "[8,9]." ]

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[ "5q22.2-5q23.1" ]

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[ "Mutation", "analysis", "of", "the", "exon", "1", "fragment", "of", "the", "K-ras", "oncogene,", "spanning", "codons", "8–29,", "was", "performed", "on", "archival", "colorectal", "adenocarcinoma", "specimens", "of", "737", "patients,", "using", "nested", "PCR,", "followed", "by", "direct", "sequencing", "of", "purified", "fragments", "[27].", "The", "detection", "limit", "was", "5%", "mutated", "DNA", "and", "duplicate", "experiments", "revealed", "a", "good", "reproducibility", "(88%)", "[27]." ]

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[ "In", "previous", "studies", "of", "KRAS", "in", "colorectal", "adenomas,", "mutation", "has", "been", "associated", "negatively", "with", "flat", "and", "depressed", "TAs", "and", "positively", "with", "polypoid", "appearance,", "increasing", "size", "adenoma", ".", "The", "current", "study", "includes", "additional", "types", "of", "polyp", "that", "are", "likely", "to", "have", "malignant", "potential,", "namely", "serrated", "polyps", "with", "(MP", "and", "SA)", "and", "without", "(SSA)", "dysplasia.", "This", "discussion", "will", "focus", "first", "on", "adenomas,", "second", "on", "non-dysplastic", "serrated", "polyps", "and", "will", "then", "conclude", "with", "the", "concept", "that", "features", "of", "these", "two", "types", "of", "polyp", "can", "co-occur", "or", "become", "‘fused’", "in", "subtypes", "of", "advanced", "polyps", "with", "mixed", "cytomorphology", "(hyperplastic", "and", "dysplastic)", "and", "a", "serrated", "and/or", "villous", "architecture." ]

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[ "The", "study", "of", "mRNA", "levels", "was", "the", "next", "step", "in", "the", "line", "of", "investigation", "of", "the", "cause", "of", "disease", "in", "patients", "with", "no", "detected", "APC", "mutation.", "Family", "1", "is", "the", "largest", "kindred", "in", "the", "Swedish", "Polyposis", "Registry;", "this", "family", "includes", "150", "individuals", "of", "whom", "57", "are", "affected", "by", "the", "disease", "(Figure", "6", "shows", "part", "of", "the", "pedigree).", "However,", "no", "pathogenic", "mutation", "had", "been", "detected", "after", "screening", "the", "whole", "coding", "region", "of", "the", "APC", "gene", "but", "as", "the", "family", "did", "show", "positive", "linkage", "to", "the", "APC", "locus", "we", "decided", "to", "perform", "expression", "analyses", "and", "evidence", "of", "lowered", "APC", "expression", "was", "obtained", "by", "quantitative", "real-time", "PCR", "(Figure", "5A).", "The", "result", "was", "supported", "by", "the", "indication", "of", "a", "lower", "expression", "from", "the", "T-allele", "from", "analysis", "of", "the", "APC", "c.5465A", ">", "T", "polymorphism", "in", "the", "cDNA", "sequencing", "diagram", "of", "two", "affected", "family", "members", "(Figure", "5B).", "The", "search", "for", "mutations", "in", "the", "DNA", "sequence", "of", "the", "APC", "promoters", "has", "been", "initiated,", "but", "no", "pathogenic", "change", "has", "been", "detected", "to", "this", "date.", "The", "possibility", "of", "the", "pathogenic", "change", "being", "epigenetic", "will", "have", "to", "be", "investigated", "further.", "Hypermethylation", "of", "CpG", "sites", "in", "the", "promoter", "of", "APC", "has", "been", "reported", "as", "a", "means", "of", "gene", "silencing", "in", "colorectal", "tumors", "[46-49].", "To", "the", "best", "of", "the", "authors'", "knowledge", "no", "germ-line", "inactivation", "of", "APC", "caused", "by", "promoter", "hypermethylation", "has", "been", "reported.", "However,", "cases", "of", "pathogenic", "germline", "epimutations", "have", "been", "identified", "in", "the", "MLH1", "gene,", "which", "causes", "hereditary", "non-polyposis", "APC", " ", "caused", "by", "promoter", "hypermethylation", "has", "been", "reported.", "However,", "cases", "of", "pathogenic", "germline", "epimutations", "have", "been", "identified", "in", "the", "MLH1", "gene,", "which", "causes", "hereditary", "non-polyposis", "CRC", "[50,51]." ]

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[ "Different", "genotype-phenotype", "correlations", "in", "FAP", "have", "been", "suggested", "[26-28].", "The", "classic", "phenotype", "is", "primarily", "caused", "by", "mutations", "in", "the", "central", "part", "of", "the", "APC", "gene.", "Mutations", "around", "codon", "1309", "cause", "a", "severe", "course", "of", "disease", "with", "early", "onset", "and", "profuse", "polyposis.", "The", "milder,", "attenuated", "form", "of", "disease", "(AFAP),", "characterized", "by", "less", "than", "100", "adenomas", "profuse", "polyposis", "disease", "MAP", " ", "is", "caused", "by", "biallelic", "mutations", "in", "the", "MUTYH", "(mutY", "homologue;", "MIM*604933)", "gene", "(1p32.1-p34.3)", "and", "is", "inherited", "in", "a", "recessive", "manner", "[4,5]." ]

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[ "Activation", "of", "the", "Wnt", "pathway", "plays", "a", "central", "role", "in", "the", "aetiology", "of", "most", "colorectal", "cancers", "and", "is", "often", "the", "result", "of", "mutations", "in", "the", "N-terminal", "domain", "of", "the", "APC", "gene,", "that", "lead", "to", "partial", "or", "complete", "loss", "of", "this", "region", "and", "thereby", "to", "loss", "of", "the", "β-catenin", "regulating", "function", "[5,6].", "Conversely,", "in", "tumours", "lacking", "these", "APC", "mutations", "[7],", "activating", "missense", "mutations", "at", "one", "of", "the", "phosphorylation", "sites", "at", "codons", "31,", "33,", "37", "and", "45", "of", "exon", "3", "of", "the", "CTNNB1", "gene", "(encoding", "the", "β-catenin", "protein)", "can", "render", "it", "stable", "as", "it", "can", "no", "longer", "be", "tagged", "for", "cellular", "degradation.", "Activation", "of", "the", "Ras", "pathway", "in", "cancer", "is", "marked", "by", "the", "loss", "of", "the", "intrinsic", "GTPase", "activity", "of", "the", "Ras", "protein,", "which", "can", "be", "ascribed", "to", "missense", "mutations", "in", "codons", "12", "and", "13", "of", "exon", "1,", "which", "are", "responsible", "for", "90%", "activating", "mutations", "in", "the", "of", "the", "K-ras", "gene", "[8]." ]

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[]

[]

[]

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[ "Not", "unexpected,", "we", "found", "loss", "of", "expression", "in", "region", "5q22.2-5q23.1", "(see", "Figures", "27,", "28,", "29).", "This", "interval", "harbors", "two", "known", "TSGs", "in", "colon", "cancer,", "the", "adenomatous", "polyposis", "coli", "gene", "(APC)", "gene", "and", "the", "mutated", "in", "colorectal", "cancer", " ", "(MCC).", "We", "were", "not", "able", "to", "obtain", "expression", "values", "for", "APC.", "APC", "is", "located", "at", "the", "border", "of", "a", "region", "at", "5q22.2-5q22.3", "that", "harbors", "several", "drastically", "down-regulated", "genes.", "Central", "in", "this", "region", "is", "the", "MCC", "colon", "cancer", " ", "(see", "Table", "4).", "Note", "the", "expression", "down-regulation", "of", "BCL2.", "SMAD4", "(Hs.298320)", "and", "TCF4", "are", "only", "weakly", "down-regulated.", "The", "DCC", "gene", "is", "also", "located", "in", "this", "region", "between", "LOC51320", "and", "MBD2", "but", "no", "informative", "expression", "measures", "were", "obtained." ]

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[ "DNA", "from", "blood", "cells", "LS", " ", "that", "attended", "Genetic", "Counselling", "at", "the", "Cancer", "Units", "of", "the", "Elche", "and", "La", "Fe", "Hospitals,", "were", "recruited.", "The", "study", "was", "approved", "by", "the", "Ethics", "Committee", "of", "the", "Elche", "University", "Hospital." ]

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[ "DNA", "sequencing", "of", "APC", "patients", " ", "(C107,", "C257,", "and", "C505),", "negative", "for", "mutations", "in", "APC,", "were", "reported", "as", "de", "novo", "cases", "with", "no", "known", "family", "history", "of", "FAP.", "These", "patients", " ", "where", "all", "screened", "for", "APC", "mutations", "present", "as", "low-frequency", "alleles", "using", "SSCP/HD.", "We", "did", "not", "detect", "any", "signs", "of", "low-frequency", "mutations", "in", "patients", " ", "C257", "and", "C505.", "However,", "in", "patient", "C107,", "aberrant", "bands,", "possibly", "originating", "from", "formation", "of", "heteroduplexes,", "was", "detected", "by", "SSCP/HD", "in", "a", "very", "low", "fraction", "of", "her", "blood", "lymphocytes.", "The", "c.2700_2701delTC", "mutation,", "which", "results", "in", "frame", "shift", "at", "codon", "900,", "was", "found", "by", "sequencing", "of", "the", "aberrant", "bands", "excised", "from", "the", "SSCP/HD", "gel", "(Figure", "2A).", "The", "mutation", "was", "detected", "in", "approximately", "one-third", "of", "the", "analyzed", "tumor-derived", "cells", "extracted", "from", "paraffin-embedded", "tissue", "by", "DNA", "sequencing", "(Figure", "2B).", "The", "mutation", "was", "not", "detectable", "at", "all", "in", "the", "sequence", "determination", "of", "DNA", "extracted", "from", "blood", "lymphocytes", "from", "the", "patient", "(Figure", "2C)." ]

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[ "Conclusion" ]

[ 0 ]

[ "Results" ]

[ 0 ]

[ "Primers", "for", "all", "exons", "of", "MSH2,", "MLH1", "and", "MSH6", "were", "designed", "for", "PCR", "amplification", "as", "previously", "reported.", "PCR", "amplification", "was", "performed", "using", "the", "reagents", "from", "ABI", "Company,", "following", "the", "protocol", "provided", "by", "the", "company.", "After", "amplification,", "the", "PCR", "products", "were", "purified", "by", "electrophoresis", "through", "a", "1.5%", "low", "melting", "point", "agarose", "gel,", "and", "then", "were", "sequenced", "on", "an", "AB13100-Avant", "sequencer", "(Applied", "Biosystem", "Shanghai", "Division)", "using", "fluorescently", "labeled", "primers,", "following", "the", "protocols", "supplied", "by", "the", "manufacturer.", "By", "comparing", "the", "obtained", "sequence", "with", "the", "known", "sequence,", "nonsense,", "missense,", "and", "frameshift", "mutations", "were", "identified.", "Nonsense", "and", "frameshift", "mutations", "were", "considered", "pathogenic.", "All", "missense", "mutations", "were", "screened", "in", "50", "patients", " ", "with", "MSS", "colorectal", "cancer", "and", "50", "people", "without", "cancer", "or", "a", "family", "history", "of", "cancer.", "They", "were", "judged", "as", "pathogenic", "if", "they", "could", "not", "be", "found", "in", "MSS", "patients", "MSI", " ", "colorectal", " ", "cancer,", "and", "genomic", "DNA", "was", "extracted", "using", "a", "kit", "from", "Beijing", "Bio-Lab", "Materials", "Institute.", "The", "extracted", "genomic", "DNA", "was", "stored", "at", "-80°C", "until", "further", "analysis." ]

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[ "Mutation", "of", "MSH2,", "MLH1", "and", "MSH6", "genes" ]

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[ "The", "majority", "of", "UVs", "are", "missense", "mutations", "or", "small", "in-frame", "deletions.", "The", "human", "gene", "pool", "harbours", "a", "vast", "number", "of", "rare", "missense", "substitutions,", "70%", "of", "which", "are", "at", "least", "mildly", "deleterious", "[2].", "Integration", "of", "various", "lines", "of", "evidence", "may", "help", "to", "classify", "UVs.", "Information", "on:", "1)", "frequencies", "in", "cases", "and", "controls,", "2)", "co-occurrence", "(in", "trans)", "with", "deleterious", "mutations,", "3)", "co-segregation", "with", "disease", "in", "pedigrees,", "4)", "pathological", "factors,", "5)", "amino", "acid", "polarity", "or", "size,", "6)", "evolutionary", "conservation", "of", "the", "residue,", "7)", "splice", "predictions", "and", "8)", "in", "vitro", "and/or", "in", "vivo", "functional", "assays", "may", "enable", "UVs", "to", "be", "classified", "as", "pathogenic", "or", "non-pathogenic", "[3]." ]

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[ "Note:", "no", "result", "for", "KRAS", "in", "one", "sessile", "serrated", "adenoma", "(SSA)", "and", "one", "tubular", "adenoma", "(TA)", "or", "for", "BRAF", "in", "one", "TA.", "MGMT", "immunstaining", "not", "performed", "in", "15", "polyps", "(seven", "HPs,", "one", "SSA,", "one", "MP", "and", "six", "TAs)." ]

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[ "Study", "protocol" ]

[ 0, 0 ]

[ "Background" ]

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[ "Concomitant", "deleterious", "variants", "were", "detected", "in", "two", "of", "the", "families:", "one", "in", "the", "MLH1", "gene", "(c.676C>T;", "p.Arg226X)", "and", "the", "other", "in", "the", "MSH6", "gene", "(c.3013C>T;", "p.Arg1005X).", "Seventeen", "affected", "and", "unaffected", "family", "members", "from", "these", "two", "families", "were", "tested", "for", "the", "pathogenic", "and", "p.Lys618Ala", "variants." ]

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[ "Equivalent", "numbers", "of", "mutations", "regardless", "of", "clinical", "stage", "are", "consistent", "with", "recent", "speculation", "that", "an", "invasive", "potential", "is", "acquired", "early", "in", "progression", "[22],", "albeit", "only", "rare", "cells", "actually", "form", "visible", "metastases.", "Primary", "breast", " ", "cancer", "expression", "patterns", "correlate", "with", "clinical", "outcomes", "or", "metastases", "[22-25],", "suggesting", "that", "a", "propensity", "to", "spread", "is", "already", "present", "at", "the", "time", "of", "transformation.", "Alternatively,", "all", "cancers", " ", "may", "have", "the", "same", "abilities", "to", "invade", "and", "metastasize,", "with", "clinical", "stage", "dependent", "on", "random", "events", "that", "occur", "rapidly", "after", "transformation.", "A", "short", "interval", "between", "transformation", "and", "detection", "may", "help", "limit", "spread", "because", "clinical", "surveillance", "tends", "to", "detect", "localized", "colorectal", " ", "cancers", "[26-28]." ]

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[ "Mutation-detection", "frequency" ]

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[ "Pedigree", "for", "Family", "#1", "(CRC:", "Colorectal", "cancer;", "GC:", "Gastric", "cancer;", "DC:", "Duodenal", "cancer)." ]

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[ "Down-regulation", "of", "mRNA", "expression", "in", "human", "chromosomal", "region", "1p36.13-1p36.11", "(patient", "counts", "with", "coordinate", "down-regulation).", "Grayscale", "plot", "of", "cross-comparison", "of", "down-regulation", "patterns", "across", "patients", "for", "gene", "pairs", "in", "a", "particular", "region.", "Both,", "horizontal", "and", "vertical", "axes", "comprise", "the", "same", "genes", "in", "chromosomal", "order.", "In", "each", "square", "total", "counts", "of", "patients", "with", "consistent", "down-regulation", "in", "two", "genes", "are", "coded", "by", "different", "shades", "of", "gray.", "Dark", "squared", "regions", "along", "the", "diagonal", "indicate", "coordinated", "regulation", "in", "patient", "subgroups.", "Note,", "that", "many", "more", "patients", " ", "show", "down-regulation", "as", "indicated", "by", "dark", "spots", "in", "this", "plot", "than", "up-regulation", "as", "indicated", "by", "dark", "spots", "in", "Figure", "10.", "This", "region", "has", "been", "reported", "in", "other", "studies", "to", "be", "frequently", "deleted", "in", "colorectal", "cancer", "(see", "Table", "4).", "This", "is", "the", "most", "significantly", "down-regulated", "region", "of", "our", "analysis.", "Note", "the", "expression", "of", "potential", "tumor", "genes", "PLA2G2A,", "E2F2,", "and", "CDC42." ]

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[ "Aberrant", "expression", "of", "p53", "and", "correlation", "with", "MGMT", "loss" ]

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[ "To", "establish", "and", "explain", "the", "pattern", "of", "molecular", "signatures", "across", "colorectal", "polyps." ]

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[ "Splice-site", "affecting", "mutations" ]

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[ "Hereditary", "nonpolyposis", "colorectal", "cancer", "(HNPCC)", "is", "an", "autosomal", "dominant", "syndrome.", "The", "National", "Cancer", "Institute", "(NCI)", "has", "recommended", "the", "Revised", "Bethesda", "guidelines", "for", "screening", "HNPCC.", "There", "has", "been", "a", "great", "deal", "of", "research", "on", "the", "value", "of", "these", "tests", "in", "other", "countries.", "However,", "literature", "about", "the", "Chinese", "population", "is", "scarce.", "Our", "objective", "is", "to", "detect", "and", "study", "microsatellite", "instability", "(MSI)", "and", "mismatch", "repair", "(MMR)", "gene", "germline", "mutation", "carriers", "among", "a", "Chinese", "population", "with", "colorectal", "cancer." ]

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[ "Individual", "chromosomal", "islands", "of", "up-", "or", "down-regulation." ]

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[ "**", "IGNORE", "LINE", "**" ]

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