Novel mutations and sequence variants in exons 3-9 of human T cell factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability.
OBJECTIVE
To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI).


METHODS
Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used.


RESULTS
Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls.


CONCLUSIONS
Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H.
Meng
Wen-Jian
WJ
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China.
Wang
Ling
L
Tian
Chao
C
Yu
Yong-Yang
YY
Zhou
Bing
B
Gu
Jun
J
Xia
Qing-Jie
QJ
Sun
Xiao-Feng
XF
Li
Yuan
Y
Wang
Rong
R
Zheng
Xue-Lian
XL
Zhou
Zong-Guang
ZG
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein