title: A novel c. 204 Ile68Met germline variant in exon 2 of the mutL homolog 1 gene in a colorectal cancer patient.
abstract: Mutations in the mutL homolog 1 (MLH1)gene are frequent in patients with hereditary non-polyposis colorectal cancer (CRC). The MLH1 gene was screened for mutations in patients with sporadic CRC. The nucleotide sequences for all 19 exons ofMLH1were analyzed by high resolution melting and sequenced in a group of 104 sporadic CRC patients, and the results were verified in a replication group of 1,095 patients and 1,469 controls. Different melting profiles for exon 2 of theMLH1gene were observed in the germline DNA of one patient. Sequencing of the patient's DNA resulted in the identification of a heterozygous C>G variant at c.204, which resulted in an Ile68Met change in the amino acid. A detailed search of the National Center for Biotechnology Information and the 1000 Genomes databases indicated that the detected variant was unique. According to the SIFT and PolyPhen-2 algorithms, the substitution of Ile to Met was predicted to decrease the activity of the MLH1 protein. The newly identified, functional germline variant was not present in any other CRC patient or control. Thus, a novel germline variant in theMLH1gene was identified, representing a rare event in sporadic CRC. The occurrence and relevance of this mutation in other types of cancer requires additional investigation.
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic ; Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.affiliation: Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic.
authors.forename: Fabian
authors.initials: F
authors.lastname: Caja
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic ; Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Vymetalkova
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic ; Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Prochazka
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic ; Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic ; Department of Toxicogenomics, National Institute of Public Health, Prague 10042, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.affiliation: Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Schwarzova
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic ; Department of Molecular Genetics, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague 12800, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg 69121, Germany.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Surgery, General University Hospital in Prague, Prague 12800, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schneiderova
keywords: MutL homolog 1; colorectal cancer; germline mutation