PTEN/MMAC1 mutations in hepatocellular carcinomas.
Mutations in the PTEN/MMAC1 gene have been identified in several types of human cancers and cancer cell lines, including brain, endometrial, prostate, breast, thyroid, and melanoma. In this study, we screened a total of 96 hepatocellular carcinoma (HCC) samples from Taiwan, where HCC is the leading cancer in males and third leading cancer in females, for mutations in the PTEN/MMAC1 gene. Complete sequence analysis of these samples demonstrated a missense mutation in exon 5 (K144I) and exon 7 (V255A) from HCC samples B6-21 and B6-2, respectively. A putative splice site mutation was also detected in intron 3 from sample B6-2. Both B6-21 and B6-2 were previously shown to contain missense mutations in the coding sequences of the p53 gene. Functional studies with the two missense mutations demonstrated that while mutation V255A in exon 7 resulted in a loss of phosphatase activity, mutation K144I in exon 5 retained its phosphatase activity. Additionally, we identified a silent mutation (P96P) in exon 5 of the PTEN/MMAC1 gene from HCC sample B6-22. These data provide the first evidence that the PTEN/MMAC1 gene is mutated in a subset of HCC samples.
Yao
Y J
YJ
Department of Dermatology, School of Public Health, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Ping
X L
XL
Zhang
H
H
Chen
F F
FF
Lee
P K
PK
Ahsan
H
H
Chen
C J
CJ
Lee
P H
PH
Peacocke
M
M
Santella
R M
RM
Tsou
H C
HC
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human