title: Effects of PTEN gene alteration in patients with gallbladder cancer.
abstract: Gallbladder cancer (GBC) is an aggressive malignancy usually diagnosed in an advanced stage. We investigated the effects of alterations of the phosphatase and tensin homologue (PTEN) gene on the occurrence and development of GBC, which has not been previously reported. A total 141 cases of GBC were analyzed for mutation, expression, and methylation across the nine exons of the PTEN gene. DNA sequencing methods were applied for mutation detection, whereas protein expression and methylation status were evaluated by immunohistochemical and methylation-specific PCR analysis, respectively. Novel PTEN mutations were observed in 6.3% of cases (9/141), and they included two silent mutations. In mutant cases, according to changes in codons, the respective amino acid sequences were also changed, which caused of proteins. A high percentage (72%) of loss of protein expression was observed more often in cases than in control samples. Interestingly, all nine cases with mutations showed loss of PTEN expression, whereas four of these nine cases showed positive promoter methylation. Hypermethylation was significantly more common in older patients than in younger ones (P<0.02). These findings suggest that PTEN mutations and inactivation may play an important role in the development and progression of gallbladder carcinoma.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Patna, India.
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Gastrointestinal Surgery, G.B. Pant Hospital, New Delhi, India.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Mishra
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Patna, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Gastrointestinal Surgery, G.B. Pant Hospital, New Delhi, India.
authors.forename: Asit
authors.initials: A
authors.lastname: Arora
authors.affiliation: Department of Gastrointestinal Surgery, G.B. Pant Hospital, New Delhi, India. Electronic address: drsundeepsaluja@gmail.com.
authors.forename: Sundeep Singh
authors.initials: SS
authors.lastname: Saluja
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005706:Gallbladder Neoplasms / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; gallbladder cancer; hypermethylation and single-strand conformation polymorphism; immunohistochemistry; mutation