A Study Of Frequent Somatic Mutations In 24 Colorectal Patient-derived Tumor Xenografts Models

Background and Objective:Colorectal cancer is one of the most common diseases cause to death worldwide,with a third morbidity.And that in China has a rising trend.Early diagnosis,treatment strategies and therapeutic evaluation are important for improving the prognosis among colorectal cancer patients.The occurrence and development of colorectal cancer are regulated by multiple genes and epigenetic alterations.Many research have proved colorectal cancer is closely associated with genetic mutations such as oncogene KRAS and BRAF,cancer suppressor gene TTP53 and APC.The Ion Torrent high-throughput sequencing,combined with Cancer Panel of 50 known oncogenes and tumor suppressor genes,benefit a lot to the research on colorectal cancer.Cancer research need animal-tumor model which can faithfully recapitulate human tumor biology and minimum genetic drift,and patient-derived tumor xenografts model is quite trustworthy.In this study,we use colorectal PDX model to detect frequent somatic mutations,and probe into the correlation between gene mutation and growth of PDX models.Experimental summary and methods:1.We collected fresh tumor tissue of 24 colorectal cancer patients after surgery,establishing PDX models.2.Get samples from the PDX models and use Ion Torrent to detected frequent somatic mutations.3.Statistical analysis to the detected mutations,comparing to COSMIC database.4.Screen frequent gene,exploring the correlation between mutations and the growth of PDX models.Results:1.We find 24 frequent mutation genes,the most frequent genes TTP53,KRAS,APC,PIK3CA are similar to COSMIC database.2.NOTCH1 and KDR mutation frequencies are high in our cohort,maybe we can use them for drug sensitivity research.3.Clinical significances are not correlated with growth of PDX models in our cohort.4.KRAS mutation can significantly accelerate the growth rate of PDX models(p=0.007),while none correlations are found in other mutations.Conclusion:1.Detect the somatic mutations of PDX models by cancer panel can promote personalized medicine,benefitting treatment strategies and therapeutic evaluation.2.The growth rate of 24 PDX models have no significant correlation with the clinical significance.3.We found KRAS mutation significantly accelerate the growth rate of PDX models,confirming its' the role in colorectal cancer.