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Non‐Hodgkin lymphoma related to hereditary nonpolyposis colorectal cancer in a patient with a novel heterozygous complex deletion in the MSH2 gene
Author(s) -
Pineda M.,
Castellsagué E.,
Musulén E.,
Llort G.,
Frebourg T.,
BaertDesurmont S.,
González S.,
Capellá G.,
Blanco I.
Publication year - 2008
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20536
Subject(s) - msh2 , microsatellite instability , cancer research , dna mismatch repair , mlh1 , germline mutation , lymphoma , colorectal cancer , biology , multiplex ligation dependent probe amplification , lynch syndrome , cancer , mutation , exon , medicine , gene , genetics , allele , pathology , microsatellite
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. © 2008 Wiley‐Liss, Inc.