TY  - JOUR
AU  - Staffa, Laura
AU  - Echterdiek, Fabian
AU  - Nelius, Nina
AU  - Benner, Axel
AU  - Werft, Wiebke
AU  - Lahrmann, Bernd
AU  - Grabe, Niels
AU  - Schneider, Martin
AU  - Tariverdian, Mirjam
AU  - von Knebel Doeberitz, Magnus
AU  - Bläker, Hendrik
AU  - Kloor, Matthias
TI  - Mismatch repair-deficient crypt foci in Lynch syndrome-molecular alterations and association with clinical parameters.
JO  - PLoS one
VL  - 10
IS  - 3
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - DKFZ-2017-03572
SP  - e0121980 -
PY  - 2015
AB  - Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients) was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12). Microsatellite instability of at least one tested marker was detected in 89
KW  - AIM2 protein, human (NLM Chemicals)
KW  - ASTE1 protein, human (NLM Chemicals)
KW  - Adaptor Proteins, Signal Transducing (NLM Chemicals)
KW  - BAX protein, human (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - MLH1 protein, human (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Proteins (NLM Chemicals)
KW  - bcl-2-Associated X Protein (NLM Chemicals)
KW  - MSH2 protein, human (NLM Chemicals)
KW  - MutL Protein Homolog 1 (NLM Chemicals)
KW  - MutS Homolog 2 Protein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25816162
C2  - pmc:PMC4376900
DO  - DOI:10.1371/journal.pone.0121980
UR  - https://inrepo02.dkfz.de/record/127549
ER  -