High frequency of G/C transversion on p53 gene alterations in breast cancers from Taiwan.
p53 gene mutation is a very frequent event in many human cancers and is associated with a poor clinical outcome in breast cancer patients. Analysis of p53 gene mutations can also provide clues to the etiology of tumor formation. The present study was conducted to investigate the p53 mutations in patients with breast cancer from Taiwan. Tumor samples from 119 patients undergoing mastectomy for breast cancer were evaluated. The mutational status of the p53 gene (exons 5-8) was screened by polymerase chain reaction-single strand conformation polymorphism analysis followed by direct sequencing. Of all 119 cases of breast carcinoma, 26 mutations of the p53 gene were found in 22 cases (18.5%). Among these mutations, 78% (20/26) were point mutations with the majority of those being missense mutations (75%, 15 of 20 mutations) and the other 22% (6/26) were frameshift mutations. No significant correlation between p53 mutations and clinicopathological features was found, including HER2 status. Moreover, our results disclosed distinct mutation spectra in excess transversions to transitions (15/21, 71.4% vs. 6/21, 28.6%) with GC to CG dominant (6/15, 40%). Mutation hot spots we identified at codons 167, 185, 186, 210, 265 and 295 have rarely been documented in the literature. These findings showed that p53 gene mutation might contribute to the pathogenesis of breast carcinoma. Furthermore, the different mutation spectrum with high transversions in G:C to C:G may imply that the exogenous mutagens outweigh the endogenous processes in breast cancer in patients in Taiwan.
Chen
Fang-Ming
FM
Department of Surgery, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC.
Hou
Ming-Feng
MF
Wang
Jaw-Yuan
JY
Chen
Tsung-chi
TC
Chen
David C P
DC
Huang
Sung-Yu
SY
Chung
Yi-Shu
YS
Lin
Shiu-Ru
SR
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013624:Taiwan; D016896:Treatment Outcome
D003062:Codon; D018719:Erb-b2 Receptor Tyrosine Kinases