Colorectal cancer without high microsatellite instability and chromosomal instability--an alternative genetic pathway to human colorectal cancer.
At least two forms of genomic instability have been described in colorectal cancers (CRCs): microsatellite instability (MIN), which is characterized by a high frequency of microsatellite instability (MSI-H) and chromosomal instability (CIN), which is characterized by losses and gains of chromosomes (aneuploidy), as well as chromosome rearrangements. Morphological and molecular heterogeneity within MIN(-) CRCs have been described, but the distinctions between MIN(-) tumors with CIN and those without CIN remain largely unknown. We studied 179 colorectal cancers to elucidate the clinicopathological characteristics and molecular events in CRCs arising along these pathways. Loss of heterozygosity, MIN, DNA content, mutation of p53 and K-ras, and expression of p53, hMLH1 and hMSH2 were examined. We found that a subtype of tumors (17%) with MIN(-) and CIN(-), differed from MIN(-)CIN(+) tumors with respect to clinicopathological and genetic characteristics. This subtype was associated with a greater frequency of poorly differentiated and/or mucinous tumors (26%). This subtype of tumors had an extremely low p53 gene mutation rate (11%) and a relatively high p53 protein accumulation rate (55%). The dissociation between the p53 gene mutation and protein accumulation suggests that stabilization of p53 protein in the absence of p53 gene mutation may be an important event on a distinct pathway.
Tang
Reiping
R
Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Lin-ko, Taiwan.
Changchien
Chung Rong
CR
Wu
Meng-Chih
MC
Fan
Chung-Wei
CW
Liu
Kwang-Wen
KW
Chen
Jinn-Shiun
JS
Chien
Huei-Tzu
HT
Hsieh
Ling-Ling
LL
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000782:Aneuploidy; D002352:Carrier Proteins; D002453:Cell Cycle; D002454:Cell Differentiation; D043171:Chromosomal Instability / Q000235:genetics*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D011905:Genes, ras; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein