[Fenotypical diversity of hereditary non-polyposis colorectal carcinoma. Pedigree and genetical analysis of two mutation carrier patients].
BACKGROUND
The phenotype of HNPCC shows great diversity. Investigation of the disease needs the application of both the Amsterdam and Bethesda Guidelines. The clinical diagnosis of HNPCC can be established by means of thorough family history containing more generations. The immunohistochemistry and MSI investigation of the tumorous tissue as well as the detection of mutations based on DNA sequencing could reinforce the existence of the possible hereditary tendency.


METHODS
Two pedigrees were selected based on the above-mentioned protocol at the Surgical Institute of the University of Debrecen, Medical and Health Science Center. Amongst first-degree relatives of the 31-year old male patient suffering from colorectal carcinoma (1st patient), three other colorectal, one gastric, one breast and one lung tumors have been found. Two genetic alterations of hMSH2 gene were detected in this family, which were also detectable in other family members. The mutation of exon 7 was not at that time available in international databases, so it was detected by us for the first time. We were able to find alterations of both hMLH1 and hMSH2 genes in the case of the 25-year old patient with synchronous colorectal carcinomas (2nd patient). These alterations could be detected in other family members as well. The whole pedigree contains only one other case of colorectal carcinoma besides the index person.


CONCLUSIONS
Several HNPCC families would be missed in case of considering the Amsterdam Criteria alone. The application of the Bethesda Guidelines is absolutely necessary for the detection of families with poor history at the first screening. The association of a polymorphism and a pathogen mutation in one person could lead to early onset of colorectal carcinoma.
Tanyi
Miklós
M
mtanyi@hotmail.com
Kanyári
Zsolt
Z
Juhász
Balázs
B
Lukács
Géza
G
Olasz
Judit
J
Kámory
Eniko
E
Csuka
Orsolya
O
Tóth
László
L
Damjanovich
László
L
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein