title: Genetic analysis of microsatellite markers in patients from hereditary nonpolyposis colorectal cancer (HNPCC) families.
abstract: OBJECTIVE
  Microsatellite instability (MSI) is due to defective DNA mismatch repair (MMR) and is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC) tumors. The role of MSI in familial predisposition to colorectal cancer was investigated in this study by both microsatellite analysis and mutation screening of the two major MMR genes MLH1 and MSH2 among familial cases.
  
  
  METHODS
  PCR-based microsatellite analysis was performed in blood obtained from 30 members from HNPCC families. Blood samples age matched healthy individuals (n = 28) served as control. MSI was studied at five loci containing single- or dinucleotide repeat sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12), BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12).
  
  
  RESULTS
  MSI frequency was higher in member of HNPCC families [7/30 (23%)] than in control [3/28 (10.7%)] cases. Two MLH1 and one MSH2 mutations were identified in 7 MSI positive samples from HNPCC families. MLH1/MSH2 mutations were only in MSI high samples detected.
  
  
  CONCLUSIONS
  Genetic alterations seem to be a risk factor of colorectal cancer in subjects belonged to HNPCC families with high incidence of this cancer.
authors.affiliation: Laboratory of Molecular Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland. smolbea@wp.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Smolarz
authors.forename: Hanna
authors.initials: H
authors.lastname: Romanowicz-Makowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Langner
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kozlowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kulig
authors.forename: Adam
authors.initials: A
authors.lastname: Dziki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001943:Breast Neoplasms / Q000235:genetics; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D018900:Dinucleotide Repeats; D005260:Female; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000235:genetics; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein