ABSTRACT
Background: Discovery of novel biomarkers of prognosis and drug response remains an elusive, yet critical goal. Thus, accurate and rapid screening of an array of pertinent mutations/SNPs is an essential step in cancer management. Methods: Using a high-throughput multiplex PCR microarray technique, we simultaneously screened the mutational status/SNP of 32 hotspots in multiple genes for metastatic colorectal cancer (mCRC) from 126 formalin fixed paraffin embedded samples from 78 patients. The efficacy of the technology was validated by cross-comparison with conventional Sanger sequencing and pyrosequencing. The clinical outcome was corroborated to the mutational status to determine prognostic and predictive significance of the 32 loci. Results: In a statistically robust multivariate model, patients with the TT genotype of the MGMT gene (rs1625649) enjoyed a significantly longer survival (61.8 months) when compared to those with GG or heterozygous GT genotype (29.3 months) [HR 0.30; 95% CI: 0.10-0.89, P= 0.03], with a 70% reduced risk of death from mCRC. Conclusion: The rs1625649 SNP within MGMT is a novel and potentially valuable prognostic biomarker for mCRC patients.
ABSTRACT
Aim: Gallbladder cancer is an aggressive malignancy usually diagnosed at late stage. The molecular genetics of this cancer is heterogeneous and not well established. Mutation profi ling of gallbladder cancer was performed through massarray technology with an aim to identify molecular markers involved in the tumor pathogenesis that can be helpful as markers for early diagnosis and targets for therapy. Materials and Methods: Forty nine cases of gallbladder cancer were screened through Sequenom Massarray technology for 390 mutations across 30 genes in formalin fi xed paraffi n embedded archived tissues and the results of mutation profi ling was correlated with tumor characteristics. Mutations were observed in 9 of 49 cases across four genes – TP53 (four cases), CTNNB1 (two cases), PIK3CA (two cases), and KRAS (one case). Six of these cases were well differentiated but of eight of them belonged to stage II to IV disease. Six cases had associated gallstones. Conclusion: The mutation frequency found in gallbladder cancer is comparable to the data available in literature. Identifi cation of PIK3CA and KRAS mutations would help in formulating more effi cacious targeted approach for management. Studies with large number of cases would help in exploring more targets and better classifi cation of these cancers at genetic level.