The differentially mutational spectra of the APC, K-ras, and p53 genes in sporadic colorectal cancers from Taiwanese patients.
OBJECTIVE
Adenomatous polyposis coli (APC), K-ras and p53 gene mutations are the most common genetic alterations present in colorectal cancer (CRC). The aim of this study was to analyze tumor mutation frequencies and spectra in a large cohort of Taiwanese patients with CRC.


METHODS
APC, K-ras, and p53 gene mutations in primary tumor tissues and their paired normal tissues of 123 CRC patients were detected by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing.


RESULTS
Of these 123 CRC patients, 43.1%, 44.7%, 35% of tumor tissue specimens presented mutations in APC, K-ras, and p53 genes, respectively. Overall, gene mutations in APC, K-ras and/or p53 were present in 78% (96/123) of tumor tissues. Among 96 CRC patients harboring gene mutations, 49 (51%) contained mutations of at least two different genes and 47 (49%) contained mutations of one gene only. The most common combination of gene mutations was APC and K-ras mutations (21.9%), followed by K-ras and p53 mutations (12.5%) and then APC and p53 mutations (10.4%). In addition, there were only 6.3% (6/96) of tumor tissues from CRC patients simultaneously containing mutations of APC, K-ras and p53 genes. The most common mutation spectrum of these genes was missense mutations, at a frequency of 38.8%, 92.7% and 70.5% for APC, K-ras and p53 genes, respectively.


CONCLUSIONS
These data support that the frequencies and patterns of somatic mutation of the APC, Kras and p53 genes in CRCs are considerably variable and distinct among populations, for which the interaction between exogenous environmental factors and endogenous gene alterations may be important determinants.
Wang
Jaw-Yuan
JY
Department of Surgery, Kaohsiung Medical University Hospital, Taiwan.
Hsieh
Jan-Sing
JS
Lu
Chien-Yu
CY
Yu
Fang-Jung
FJ
Wu
Jeng-Yih
JY
Chen
Fang-Ming
FM
Huang
Che-Jen
CJ
Lin
Shiu-Ru
SR
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D013624:Taiwan