Analysis of PTEN gene mutations in Korean patients with Cowden syndrome and polyposis syndrome.
OBJECTIVE
PTEN (phosphatase and tensin homologue deleted in chromosome 10) is a candidate tumor suppressor gene. Mutations of this gene are responsible for PTEN hamartoma tumor syndromes, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus -like syndromes. Recently, PTEN mutations were identified in several human neoplasms. We analyzed the DNA of various organs and lesions in Korean patients with Cowden syndrome, their family members, and patients with familial adenomatous polyposis for germline or somatic PTEN mutations.


METHODS
The 11 patients included in this study were 5 patients with Cowden syndrome, 4 of their family members, and 2 patients with familial adenomatous polyposis. Deletions and mutations in exons 1 to 9 of the PTEN gene were evaluated by polymerase chain reaction-single strand conformation polymorphism and sequencing analysis in esophageal acanthosis, gastric polyps, colonic polyps, skin lesions, and peripheral blood mononuclear cells. To exclude common polymorphisms, 240 controls were tested.


RESULTS
All patients with Cowden syndrome showed several to numerous polyps in the gastrointestinal tract. A missense mutation at codon 217 (GTC to GAC, Val to Asp) in exon 7 was identified in one Cowden syndrome patient, and a nonsense mutation at codon 211 (TGC to TGA, Cys to stop) in exon 6 was identified in a second patient. Identical mutations were found in all tissue samples, including colonic polyps, from each patient. No PTEN mutations were found in their family members or in any patient with familial adenomatous polyposis. None of tested controls contained a mutation.


CONCLUSIONS
We have identified two new germline PTEN mutations in Korean patients with Cowden syndrome. Mutations in the introns and regulatory regions of the PTEN gene may be present in additional patients with Cowden syndrome and polyposis syndrome.
Kim
Dae-Kyoum
DK
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea,
Myung
Seung-Jae
SJ
Yang
Suk-Kyun
SK
Hong
Seong Soo
SS
Kim
Kyu Jong
KJ
Byeon
Jeong-Sik
JS
Lee
Gin Hyug
GH
Kim
Jin-Ho
JH
Min
Young Il
YI
Lee
Sun Mi
SM
Jeong
Jin-Yong
JY
Song
Kyuyoung
K
Jung
Sung-Ae
SA
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D004252:DNA Mutational Analysis; D005091:Exons; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D007723:Korea; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human