Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human ‘de novo’ colorectal carcinomas

Abstract

‘de novo’ carcinogenesis has been advocated besides ‘adenoma carcinoma sequence’ as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of ‘de novo’ carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the ‘de novo’ carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa ( P < 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of ‘de novo’ colorectal carcinogenesis. © 2001Cancer Research Campaign http://www.bjcancer.com

Gene expression profile by inhibiting Raf-1 protein kinase in breast cancer cells

“…In our study, AS-raf-ODN treatment has led to a maximum inhibition of glycogen phosphorylase, brain isoform (PYGB) expression. PYGB is a key enzyme in glycogen degradation for inducing an emergency glucose supply during stress and ischemia (40). Overexpression of PYGB has been reported in early stages of gastric and colorectal cancers (41).…”

Gene Expression Profile Analysis by DNA Microarrays

“…Normal-appearing tissue near a tumor could, for example, be genotypically altered or exhibit an altered gene expression profile. [10][11][12][13] Moreover, factors such as the degree of disease-associated inflammation may have a significant impact on gene expression profiles. Other bystander effects, epiphenomena, or secondary disease processes could all play important roles in determining expression profiles within these adjacent, so-called normal tissues.…”

Identification of a glycolysis‐related gene signature for survival prediction of ovarian cancer patients

“…As an oncogene, 64,65 the overexpression of DDIT4 correlates with tumor progression and worse outcomes in several human cancers, including OV 18,66–68 . Brain‐type glycogen phosphorylase ( PYGB ) could regulate multiple biological characteristics of cancer cells, such as proliferation, invasion, and apoptosis, and metastatic phenotypes of several cancers 69–74 . PYGB regulates the Wnt/β‐catenin signaling pathway to achieve cancer‐promoting effects in OV, 75 non‐small cell lung cancer, 76 and gastric cancer 77 .…”