PMID- 16855398
OWN - NLM
STAT- MEDLINE
DCOM- 20061227
LR  - 20200930
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 5
IP  - 13
DP  - 2006 Jul
TI  - Genomic instability in precancerous lesions before inactivation of tumor 
      suppressors p53 and APC in patients.
PG  - 1443-7
AB  - The etiology and significance of genomic instability (GIN), a hallmark of human 
      cancers, remains controversial. The paradigm that inactivation of tumor 
      suppressors [e.g. p53 or adenomatous polyposis coli (APC) genes] leads to GIN is 
      largely based on experiments in vitro and in animal models. It remains unclear 
      whether GIN is a cause or a result of cancer, particularly in patients. 
      Precancerous Barrett's esophagus (BE) provides a clinical model to investigate 
      GIN in cancer progression. We analyzed specimens from endoscopic biopsies or 
      esophagectomies in patients with BE (ten cases, including five cases with 
      multilayered epithelium (ME)), BE-associated esophageal adenocarcinoma (ten 
      cases), or with normal gastro-esophageal junction (five cases). Chromosomal 
      enumeration probe Cep 7, 11, 12, 17 and 18 were detected by fluorescence in situ 
      hybridization (FISH). Expression of p53 and APC were determined by 
      immunohistochemistry. Increased p53 expression, a measurement of p53 mutations, 
      was observed in BE with high grade dysplasia (HGD) and in BE-associated 
      esophageal cancer (EC). The expression of wild type APC was decreased in BE with 
      HGD and in advanced EC. Chromosomal abnormalities were found in all EC samples. 
      Numeric changes of chromosome 7, 11 and 12 were observed in BE in 14%, 64% and 
      43% of cases, respectively. Aneusomy of chromosome 11 and 12 were found in ME and 
      in BE without dysplasia, in the presence of normal expression pattern of p53 and 
      APC. Our results suggest that GIN is an early event that occurs at precancerous 
      stages prior to changes in tumor suppressor genes (p53 and APC) in BE-associated 
      tumorigenesis in patients, suggesting that GIN may serve as a causative link 
      between chronic inflammation and cancer.
FAU - Yang, Youxin
AU  - Yang Y
AD  - Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard 
      Medical School, Boston, Massachusetts 02215, USA. yyang@BIDMC.harvard.edu
FAU - Fruehauf, Johannes
AU  - Fruehauf J
FAU - Xiang, Shuanglin
AU  - Xiang S
FAU - Li, Chiang J
AU  - Li CJ
LA  - eng
PT  - Journal Article
DEP - 20060701
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein/genetics/*metabolism
MH  - Chromosomes, Human
MH  - Gene Expression
MH  - *Genomic Instability
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Precancerous Conditions/*genetics/*metabolism/pathology
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
EDAT- 2006/07/21 09:00
MHDA- 2006/12/28 09:00
CRDT- 2006/07/21 09:00
PHST- 2006/07/21 09:00 [pubmed]
PHST- 2006/12/28 09:00 [medline]
PHST- 2006/07/21 09:00 [entrez]
AID - 2897 [pii]
AID - 10.4161/cc.5.13.2897 [doi]
PST - ppublish
SO  - Cell Cycle. 2006 Jul;5(13):1443-7. doi: 10.4161/cc.5.13.2897. Epub 2006 Jul 1.