Promyelocytic Leukemia (PML) Gene Mutations may not Contribute to Gastric Adenocarcinoma Development.
Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail : ghafourifard@razi.tims.ac.ir.
Zeinab
Z
Imani-Saber
Ehsan
E
Yousefi-Razin
Mona
M
Javaheri
Reza
R
Mirfakhraie
Gholamreza
G
Motalleb
Soudeh
S
Ghafouri-Fard
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004586:Electrophoresis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human