ABSTRACT
Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.
ABSTRACT
Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.
ABSTRACT
The prevalence of metabolic syndrome (MS) in the nonobese population is not low. However, the identification and risk mitigation of MS are not easy in this population. We aimed to develop an MS prediction model using genetic and clinical factors of nonobese Koreans through machine learning methods. A prediction model for MS was designed for a nonobese population using clinical and genetic polymorphism information with five machine learning algorithms, including naïve Bayes classification (NB). The analysis was performed in two stages (training and test sets). Model A was designed with only clinical information (age, sex, body mass index, smoking status, alcohol consumption status, and exercise status), and for model B, genetic information (for 10 polymorphisms) was added to model A. Of the 7,502 nonobese participants, 647 (8.6%) had MS. In the test set analysis, for the maximum sensitivity criterion, NB showed the highest sensitivity: 0.38 for model A and 0.42 for model B. The specificity of NB was 0.79 for model A and 0.80 for model B. In a comparison of the performances of models A and B by NB, model B (area under the receiver operating characteristic curve [AUC] = 0.69, clinical and genetic information input) showed better performance than model A (AUC = 0.65, clinical information only input). We designed a prediction model for MS in a nonobese population using clinical and genetic information. With this model, we might convince nonobese MS individuals to undergo health checks and adopt behaviors associated with a preventive lifestyle.