title: Non-Hodgkin lymphoma related to hereditary nonpolyposis colorectal cancer in a patient with a novel heterozygous complex deletion in the MSH2 gene.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal disorder caused by mutations in DNA mismatch repair (MMR) genes. Tumors of the HNPCC-spectrum are associated with microsatellite instability (MSI) and loss of MMR protein expression. Lymphomas are not considered to be HNPCC-related tumors. We report and analyze a case of an HNPCC patient with three colorectal cancers and a B-cell non-Hodgkin lymphoma. Quantitative multiplex PCR of short fluorescent fragments detected a novel MSH2 rearrangement involving exons 9 and 10, which proved to be the pathogenic cause of the disease in the family. Tumor tissues including the lymphoma showed MSI and loss of MSH2 expression. Multiplex ligation-dependent probe amplification analysis revealed a somatic loss of the wild-type MSH2 allele in the lymphoma. These results support the fact that the total loss of a MMR gene can lead to lymphomagenesis, as seen in biallelic MMR-deficient families and knockout mice. Moreover, this is the first report of a B-cell non-Hodgkin lymphoma with a loss of the MSH2 protein expression, linked to a heterozygous germline MSH2 mutation in an HNPCC family.
authors.affiliation: Translational Research Laboratory, IDIBELL- Institut Català d'Oncologia, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pineda
authors.forename: E
authors.initials: E
authors.lastname: Castellsagué
authors.forename: E
authors.initials: E
authors.lastname: Musulén
authors.forename: G
authors.initials: G
authors.lastname: Llort
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
authors.forename: S
authors.initials: S
authors.lastname: Baert-Desurmont
authors.forename: S
authors.initials: S
authors.lastname: González
authors.forename: G
authors.initials: G
authors.lastname: Capellá
authors.forename: I
authors.initials: I
authors.lastname: Blanco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D006801:Humans; D016393:Lymphoma, B-Cell / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein