Analysis of the PTEN gene mutation in polyposis syndromes and sporadic gastrointestinal tumors in Japanese patients.
OBJECTIVE
PTEN is a candidate tumor suppressor gene for mutations which are responsible for Cowden disease. Recently, it has been shown that PTEN is mutated in several human neoplasms. To investigate the role of PTEN in tumorigenesis, we screened its mutation in Japanese patients with gastrointestinal polyposis and various sporadic tumors.


METHODS
The entire coding region of PTEN was screened by single strand conformational polymorphism or direct sequencing for somatic mutations in 16 gingival papillomas, 4 juvenile polyps, 10 esophageal papillomas, and 20 colorectal cancers and for germline mutations in three patients with Cowden disease (including one with Lhermitte-Duclos disease) and one patient each with juvenile polyposis syndrome, Turcot's syndrome, and Cronkhite-Canada syndrome.


RESULTS
Germline mutations were found in all cases of Cowden disease. One mutation was a nonsense mutation at codon 130 (CGA-->TGA), and the other two were splice site mutations at the 5' site of intron 4 and the 3' site of intron 8. We could not detect germline mutations in other patients with gastrointestinal polyposis or somatic mutations in sporadic tumors.


CONCLUSIONS
We confirmed previous reports that germline mutations in PTEN are responsible for Cowden disease. However, somatic mutations of PTEN may not play a major role in tumorigenesis, at least in colorectal cancers, esophageal papillomas and gingival papillomas.
Negoro
K
K
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Takahashi
S
S
Kinouchi
Y
Y
Takagi
S
S
Hiwatashi
N
N
Ichinohasama
R
R
Shimosegawa
T
T
Toyota
T
T
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051059:PTEN Phosphohydrolase; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human