PMID- 17373663
OWN - NLM
STAT- MEDLINE
DCOM- 20070806
LR  - 20210103
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 121
IP  - 2
DP  - 2007 Jul 15
TI  - Beta2-microglobulin mutations in microsatellite unstable colorectal tumors.
PG  - 454-8
AB  - Defects of DNA mismatch repair (MMR) cause the high level microsatellite 
      instability (MSI-H) phenotype. MSI-H cancers may develop either sporadically or 
      in the context of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome 
      that is caused by germline mutations of MMR genes. In colorectal cancer (CRC), 
      MSI-H is characterized by a dense lymphocytic infiltration, reflecting a high 
      immunogenicity of these cancers. As a consequence of immunoselection, MSI-H CRCs 
      frequently display a loss of human leukocyte antigen (HLA) class I antigen 
      presentation caused by mutations of the beta2-microglobulin (beta2m) gene. To 
      examine the implications of beta2m mutations during MSI-H colorectal tumor 
      development, we analyzed the prevalence of beta2m mutations in MSI-H colorectal 
      adenomas (n=38) and carcinomas (n=104) of different stages. Mutations were 
      observed in 6/38 (15.8%) MSI-H adenomas and 29/104 (27.9%) MSI-H CRCs. A higher 
      frequency of beta2m mutations was observed in MSI-H CRC patients with germline 
      mutations of MMR genes MLH1 or MSH2 (36.4%) compared with patients without 
      germline mutations (15.4%). The high frequency of beta2m mutations in 
      HNPCC-associated MSI-H CRCs is in line with the hypothesis that immunoselection 
      may be particularly pronounced in HNPCC patients with inherited predisposition to 
      develop MSI-H cancers. beta2m mutations were positively related to stage in 
      tumors without distant metastases (UICC I-III), suggesting that loss of beta2m 
      expression may promote local progression of colorectal MSI-H tumors. However, no 
      beta2m mutations were observed in metastasized CRCs (UICC stage IV, p=0.04). 
      These results suggest that functional beta2m may be necessary for distant 
      metastasis formation in CRC patients.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Kloor, Matthias
AU  - Kloor M
AD  - Department of Applied Tumor Biology, Institute of Pathology, University of 
      Heidelberg, Heidelberg, Germany. matthias.kloor@med.uni-heidelberg.de
FAU - Michel, Sara
AU  - Michel S
FAU - Buckowitz, Boris
AU  - Buckowitz B
FAU - Ruschoff, Josef
AU  - Ruschoff J
FAU - Buttner, Reinhard
AU  - Buttner R
FAU - Holinski-Feder, Elke
AU  - Holinski-Feder E
FAU - Dippold, Wolfgang
AU  - Dippold W
FAU - Wagner, Rudolf
AU  - Wagner R
FAU - Tariverdian, Mirjam
AU  - Tariverdian M
FAU - Benner, Axel
AU  - Benner A
FAU - Schwitalle, Yvette
AU  - Schwitalle Y
FAU - Kuchenbuch, Beate
AU  - Kuchenbuch B
FAU - von Knebel Doeberitz, Magnus
AU  - von Knebel Doeberitz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (beta 2-Microglobulin)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics
MH  - Adult
MH  - Aged
MH  - Colorectal Neoplasms/genetics/metabolism/*pathology
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Frequency
MH  - Germ-Line Mutation
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Male
MH  - Microsatellite Repeats/*genetics
MH  - Middle Aged
MH  - MutL Protein Homolog 1
MH  - MutS Homolog 2 Protein/genetics
MH  - *Mutation
MH  - Neoplasm Staging
MH  - Nuclear Proteins/genetics
MH  - beta 2-Microglobulin/*genetics/metabolism
EDAT- 2007/03/22 09:00
MHDA- 2007/08/07 09:00
CRDT- 2007/03/22 09:00
PHST- 2007/03/22 09:00 [pubmed]
PHST- 2007/08/07 09:00 [medline]
PHST- 2007/03/22 09:00 [entrez]
AID - 10.1002/ijc.22691 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Jul 15;121(2):454-8. doi: 10.1002/ijc.22691.