Abstract:
Objective To detect and investigate the somatic mutations of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) in patients with non-small cell lung cancers (NSCLCs).
Methods DNA and RNA were isolated from 182 tumor tissues obtained from the tumor bank of the Guangdong Lung Cancer Institute. The sequences of exons 1 to 9 of the PTEN gene and exons 18 to 21 of EGFR were assayed using PCR and direct sequencing. The relationships of the PTEN mutation rate with the clinical parameters were analyzed using Fisher's exact test. A two-tailed P-value of < 0.05 was considered statistically significant.
Results Eighty-one of the 182 patients had squamous cell carcinoma, 90 with adenocarcinoma, and 11 with large cell carcinoma. PTEN mutations were present in 18 (9.9%) of the 182 tumors. These mutations were observed as follows: male and female at 11.0% and 6.5% (P= 0.549), respectively; smokers and non-smokers at 13.0% and 6.7% (P= 0.15), respectively; and in patients with adenocarcinoma and squamous cell carcinoma at 7.8% and 9.9% (P= 0.628), respectively. No significant differences were observed between these mutations. PTEN mutation types were predominantly point mutation, small fragment deletion, and insertion mutation. These mutations were primarily present in exon 8. Ten mutations were all found in males and in smokers, in addition to one mutation in males and in non-smokers. However, 7 large fragment deletion mutations were found, 6 of which were in ACs. The mutation rate was 3.8% (7/182). The deleted fragments were approximately 250 to 539 bases and primarily present in exons 1 to 7. No significant relationships were observed between the large fragment deletion and gender as well as smoking habits. We found 4 large fragment deletions coupled with EGFR activating mutations.
Conclusion NSCLC with different types of PETN mutation may represent two different diseases. Large deletion mutations of PTEN may contribute to resistance to EGFR TK inhibitors in patients with mutant EGFR.
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