Premium
Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer
Author(s) -
Krüger Stefan,
Plaschke Jens,
Pistorius Steffen,
Jeske Birgit,
Haas Stephan,
Krämer Heike,
Hinterseher Irene,
Bier Andrea,
Kreuz Friedmar R.,
Theissig Franz,
Saeger Hans D.,
Schackert Hans K.
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9004
Subject(s) - mlh1 , msh2 , microsatellite instability , biology , germline mutation , missense mutation , genetics , dna mismatch repair , germline , lynch syndrome , nonsense mutation , mutation , cancer research , colorectal cancer , gene , cancer , microsatellite , allele
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent hereditary form of colorectal cancer and is caused by germline mutations in mismatch repair (MMR) genes. The majority of mutations occur in MLH1 and MSH2. We report hereby seven novel germline mutations in these two genes (five in MLH1 and two in MSH2). All mutations have been found in families fulfilling criteria of the Bethesda guidelines and four of which also fulfilled the Amsterdam criteria. We identified three insertions or deletions of 1 bp leading to premature stop codons (MLH1: c.341delC, c.1413‐1414insA; MSH2: c.1119delG) and three nonsense mutations (MLH1: c.67G>T [E23X], c.436C>T [Q146X]; MSH2: c.1857T>G [Y619X]). The corresponding tumors showed a high level of microsatellite instability (MSI‐H) and a complete loss of expression of the affected protein. In addition, a missense mutation in MLH1 was identified (c.1984A>C [T662P]). The respective tumor also showed a high level of microsatellite instability but a reduced, rather then lost, expression of the MLH1‐protein. This missense mutation was not found in 107 healthy control individuals and in 54 HNPCC patients. © 2001 Wiley‐Liss, Inc.