Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.
OBJECTIVE
The Fas-Fas ligand system is considered a major pathway for induction of apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis. There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8 in exon 7) genes that could be frameshift mutation targets in colorectal carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently harbor somatic mutations in cancers, we explored the possibility as to whether mutations of FLASH and PTPN13 are a feature of colorectal carcinomas.


METHODS
We analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)- based single-strand conformation polymorphism (SSCP).


RESULTS
We detected two mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were not frameshift (deletion or insertion) mutations in the polyadenine tracts of FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA) and a missense mutation (c.3703A>C).


CONCLUSIONS
These data indicate that frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13 mutations in the polyadenine tracts may not have a crucial role in the pathogenesis of colorectal carcinomas.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Eun Goo
EG
Jeong
Sung Hak
SH
Lee
Nam Jin
NJ
Yoo
Sug Hyung
SH
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D007723:Korea; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13