PMID- 17089045
OWN - NLM
STAT- MEDLINE
DCOM- 20061228
LR  - 20061107
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 16
IP  - 6
DP  - 2006 Dec
TI  - Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: 
      correlation to activated K-ras oncogene.
PG  - 1245-52
AB  - Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and 
      large adenoma (>1 cm). This study was intended to clarify the correlation between 
      the existence of K-ras oncogene and the pathological features of colorectal 
      adenomas using our recently developed membrane arrays. Moreover, the downstream 
      genes regulated by K-ras oncogene were explored to serve as potential biomarkers 
      in the early diagnosis and risk assessment of patients with colorectal adenoma. 
      Specimens were collected from 70 patients with colorectal adenoma. The 
      alterations of K-ras oncogene were analyzed by direct sequencing and our 
      constructed membrane arrays, respectively. The results of direct sequencing 
      showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently 
      mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras 
      oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. 
      Statistical analyses showed that the membrane array had the accuracy of 90.0%, 
      sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational 
      sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% 
      (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the 
      correlation between the experimental data and pathological characteristics of 
      adenoma showed that activated K-ras oncogenes were significantly associated with 
      the size, number and histology of adenomas (all P<0.001). Finally, we found the 
      downstream genes activated by K-ras oncogene, including B-cell CLL/lymphoma 2 
      (BCL2), Homo sapiens H2A histone family, member Z (H2AFZ), Homo sapiens RAP1B, 
      member of RAS oncogene family (RAP1B), Homo sapiens T-box 19 (TBX19), Homo 
      sapiens E2F transcription factor 4, p107/p130-binding (E2F4) and matrix 
      metallopeptidase 1 (MMP1), of which were overexpressed in most of all examined 
      adenomas. These genes were then suggested to have functions involved in cell 
      growth. The preliminary results indicated that the accuracy of membrane arrays 
      was comparable to conventional DNA sequencing in the detection of activated K-ras 
      oncogenes. Therefore, we propose that activated K-ras oncogene in colorectal 
      adenomas may play an important role in the subsequent colorectal carcinogenesis 
      through a group of K-ras-related molecular targets.
FAU - Wang, Jaw-Yuan
AU  - Wang JY
AD  - Department of Surgery, Faculty of Medicine, College of Medicine, and Kaohsiung 
      Medical University Hospital, Kaohsiung Medical University, Taipei, Taiwan.
FAU - Wang, Yung-Hsin
AU  - Wang YH
FAU - Jao, Shu-Wen
AU  - Jao SW
FAU - Lu, Chien-Yu
AU  - Lu CY
FAU - Kuo, Chao-Hung
AU  - Kuo CH
FAU - Hu, Huang-Ming
AU  - Hu HM
FAU - Hsieh, Jan-Sing
AU  - Hsieh JS
FAU - Chong, Inn-Wen
AU  - Chong IW
FAU - Cheng, Tian-Lu
AU  - Cheng TL
FAU - Lin, Shiu-Ru
AU  - Lin SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (DNA Primers)
SB  - IM
MH  - Adenoma/*genetics/*pathology
MH  - Adult
MH  - Aged
MH  - Cell Transformation, Neoplastic/genetics
MH  - Colorectal Neoplasms/*genetics/*pathology
MH  - DNA Primers
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, ras
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymerase Chain Reaction
EDAT- 2006/11/08 09:00
MHDA- 2006/12/29 09:00
CRDT- 2006/11/08 09:00
PHST- 2006/11/08 09:00 [pubmed]
PHST- 2006/12/29 09:00 [medline]
PHST- 2006/11/08 09:00 [entrez]
PST - ppublish
SO  - Oncol Rep. 2006 Dec;16(6):1245-52.