Mutational and expressional analyses of PTEN gene in colorectal cancer from Northern India.
The PTEN is a tumor-suppressor gene located on chromosome 10q23.3 and established to play key role in the varied types of cancer. To elucidate the possible effect of mutations and inactivation of PTEN gene on the occurrence and development of colorectal cancer (CRC), 223 cancer specimens were selected to probe PTEN gene mutations through the micro dissection of the genome. Polymerase chain reaction single-strand conformation polymorphism and DNA sequencing methods were applied for mutations while protein expression was evaluated by immunohistochemistry. Mutations in exons 7 and 8 of PTEN were observed in 12.5% and PTEN loss of expression was identified in 48% in CRC. In exon 7, we found the insertion of "G" resulted into the change at codon 218 from TGC to GTC leading to change in the reading frame starting downward from Cystein to Valine. In addition, the insertion of "A" in the same exon at codon 213 resulted into the change of codon CCT to CCA, which cause silent mutation. In exon 8, however, "A" is replaced by C at codon 282, but both encodes for Glycine. Statistically significant loss of PTEN expression was observed in cancerous tissue when compared with the adjacent control (P < 0.05). Furthermore, weak PTEN expression in CRC tissues were significantly associated with tumor size, depth of invasion, lymphatic invasion, lymph node metastasis, grade of differentiation, and TNM stage (P < 0.05). Our results suggested that PTEN gene mutation and loss of PTEN expression may provide valuable prognostic information to aid treatment strategies for CRC patients.
Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Asgar
A
Ali
Sundeep S
SS
Saluja
Krishnan
K
Hajela
Pramod K
PK
Mishra
Moshahid A
MA
Rizvi
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007194:India; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D015996:Survival Rate
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
PTEN gene; colorectal cancer; immunohistochemistry; mutation