PMID- 15083191
OWN - NLM
STAT- MEDLINE
DCOM- 20040526
LR  - 20220309
IS  - 0007-0920 (Print)
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 90
IP  - 8
DP  - 2004 Apr 19
TI  - Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer.
PG  - 1594-9
AB  - Our study aimed at elucidating which genetic alterations tend to form a network 
      and could be applied as molecular markers of larynx squamous cell carcinoma 
      (LSCC). A panel of genes involved in tumorigenesis was investigated. To search 
      for the possible mechanisms of gene silencing, loss of heterozygosity (LOH) was 
      analysed followed by testing DNA methylation and protein expression for those 
      genes found with the highest frequency of LOH (CDKN2A (55.4%), MLH1 (46.0%), RB1 
      (35.7%)). A correlation of both LOH and hypermethylation with the loss of 
      expression for CDKN2A and MLH1 was found. Disrupted Rb pathway (loss of 
      expression of RB1 and/or of CDKN2A) in 55.9% of analysed cases confirmed the 
      hypothesis that RB1 pathway is altered in head and neck squamous cell carcinomas, 
      with CDKN2A (45%), rather than RB1 (11.8%) being more frequently inactivated. In 
      LSCC, LOH tends to occur together in gene pairs or triplets. The pair MLH1/CDKN2A 
      and triplets MLH1/TSG on 8p22/CDKN2A and MLH1/CDKN2A/RB1 are related to staging 
      and grading. LOH in MLH1 correlates with lower and LOH in CDKN2A with higher 
      grades of LSCC. It can be concluded that MLH1 and CDKN2A play an important role 
      in LSCC development and progression.
FAU - Sasiadek, M M
AU  - Sasiadek MM
AD  - Department of Genetics, Medical University, ul. Marcinkowskiego 1, Wroclaw 
      50-368, Poland. sasiadek@gen.am.wroc.pl
FAU - Stembalska-Kozlowska, A
AU  - Stembalska-Kozlowska A
FAU - Smigiel, R
AU  - Smigiel R
FAU - Ramsey, D
AU  - Ramsey D
FAU - Kayademir, T
AU  - Kayademir T
FAU - Blin, N
AU  - Blin N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adult
MH  - Aged
MH  - Base Pair Mismatch
MH  - Biomarkers, Tumor/*analysis
MH  - Carcinoma, Squamous Cell/*genetics/*pathology
MH  - Carrier Proteins
MH  - *Cell Transformation, Neoplastic
MH  - Cyclin-Dependent Kinase Inhibitor p16/analysis/*genetics/pharmacology
MH  - DNA, Neoplasm
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, p16
MH  - Humans
MH  - Laryngeal Neoplasms/*genetics/*pathology
MH  - Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - MutL Protein Homolog 1
MH  - Neoplasm Proteins/analysis/*genetics/pharmacology
MH  - Nuclear Proteins
PMC - PMC2410272
EDAT- 2004/04/15 05:00
MHDA- 2004/05/27 05:00
PMCR- 2005/04/06
CRDT- 2004/04/15 05:00
PHST- 2004/04/15 05:00 [pubmed]
PHST- 2004/05/27 05:00 [medline]
PHST- 2004/04/15 05:00 [entrez]
PHST- 2005/04/06 00:00 [pmc-release]
AID - 6601679 [pii]
AID - 10.1038/sj.bjc.6601679 [doi]
PST - ppublish
SO  - Br J Cancer. 2004 Apr 19;90(8):1594-9. doi: 10.1038/sj.bjc.6601679.